1 1560 157 DNA METHYLATION OF ALZHEIMER DISEASE AND TAUOPATHY-RELATED GENES IN POSTMORTEM BRAIN. DNA METHYLATION OCCURS PREDOMINANTLY AT CYTOSINES THAT PRECEDE GUANINES IN DINUCLEOTIDE CPG SITES; IT IS ONE OF THE MOST IMPORTANT MECHANISMS FOR EPIGENETIC DNA REGULATION DURING NORMAL DEVELOPMENT AND FOR ABERRANT DNA IN CANCER. TO DETERMINE THE FEASIBILITY OF DNA METHYLATION STUDIES IN THE POSTMORTEM HUMAN BRAIN, WE EVALUATED BRAIN SAMPLES WITH VARIABLE POSTMORTEM ARTIFICIALLY INCREASED DELAYS UP TO 48 HOURS. DNA METHYLATION WAS ANALYZED IN SELECTED REGIONS OF MAPT, APP, AND PSEN1 IN THE FRONTAL CORTEX AND HIPPOCAMPUS OF CONTROLS (N=26) AND THOSE WITH ALZHEIMER DISEASE AT STAGES I TO II (N=17); ALZHEIMER DISEASE AT STAGES III TO IV (N=15); ALZHEIMER DISEASE AT STAGES V TO VI (N=12); ARGYROPHILIC GRAIN DISEASE (N=10); FRONTOTEMPORAL LOBAR DEGENERATION LINKED TO TAU MUTATIONS (N=6); FRONTOTEMPORAL LOBAR DEGENERATION WITH UBIQUITIN-IMMUNOREACTIVE INCLUSIONS (N=4); FRONTOTEMPORAL LOBAR DEGENERATION WITH MOTOR NEURON DISEASE (N=3); PICK DISEASE (N=3); PARKINSON DISEASE (N=8); DEMENTIA WITH LEWY BODIES, PURE FORM (N=5); AND DEMENTIA WITH LEWY BODIES, COMMON FORM (N=15). UCHL1 (UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 1 GENE) WAS ANALYZED IN THE FRONTAL CORTEX OF CONTROLS AND THOSE WITH PARKINSON DISEASE AND RELATED SYNUCLEINOPATHIES. DNA METHYLATION SITES WERE VERY REPRODUCIBLE IN EVERY CASE. NO DIFFERENCES IN THE PERCENTAGE OF CPG METHYLATION WERE FOUND BETWEEN CONTROL AND DISEASE SAMPLES OR AMONG THE DIFFERENT PATHOLOGICAL ENTITIES IN ANY REGION ANALYZED. BECAUSE SMALL CHANGES IN METHYLATION OF DNA PROMOTERS IN VULNERABLE CELLS MIGHT HAVE NOT BEEN DETECTED IN TOTAL HOMOGENATES, HOWEVER, THESE RESULTS SHOULD BE INTERPRETED WITH CAUTION, PARTICULARLY AS THEY RELATE TO CHRONIC DEGENERATIVE DISEASES IN WHICH SMALL MODIFICATIONS MAY BE SUFFICIENT TO MODULATE DISEASE PROGRESSION. 2009 2 6364 32 THE ROLE OF LONG NONCODING RNAS IN NEURODEGENERATIVE DISEASES. LONG NONCODING RNAS (LNCRNAS) ARE TRANSCRIPTS WITH LOW PROTEIN-CODING POTENTIAL BUT OCCUPY A LARGE PART OF TRANSCRIPTIONAL OUTPUT. THEIR ROLES INCLUDE REGULATING GENE EXPRESSION AT THE EPIGENETIC, TRANSCRIPTIONAL, AND POST-TRANSCRIPTIONAL LEVEL IN CELLULAR HOMEOSTASIS. HOWEVER, LNCRNA STUDIES ARE STILL IN THEIR INFANCY AND THE FUNCTIONS OF THE VAST MAJORITY OF LNCRNA TRANSCRIPTS REMAIN UNKNOWN. IT IS GENERALLY KNOWN THAT THE FUNCTION OF THE HUMAN NERVOUS SYSTEM LARGELY RELIES ON THE PRECISE REGULATION OF GENE EXPRESSION. VARIOUS STUDIES HAVE SHOWN THAT LNCRNAS HAVE A SIGNIFICANT IMPACT ON NORMAL NEURAL DEVELOPMENT AND ON THE DEVELOPMENT AND PROGRESSION OF NEURODEGENERATIVE DISEASES. IN THIS REVIEW, WE FOCUSED ON RECENT STUDIES ASSOCIATED WITH LNCRNAS IN NEURODEGENERATIVE DISEASES, INCLUDING ALZHEIMER'S DISEASE (AD), PARKINSON'S DISEASE (PD), HUNTINGTON'S DISEASE (HD), AMYOTROPHIC LATERAL SCLEROSIS (ALS), MULTIPLE SYSTEM ATROPHY (MSA), FRONTOTEMPORAL LOBAR DEGENERATION (FTLD), AND GLAUCOMA. GLAUCOMA, CAUSED BY UNEXPLAINED GANGLION CELL LESION AND APOPTOSIS, IS NOW LABELED AS A CHRONIC NEURODEGENERATIVE DISORDER [1], AND THEREFORE, WE DISCUSSED THE ASSOCIATION OF LNCRNAS WITH GLAUCOMA AS WELL. WE ILLUSTRATE THE ROLE OF SOME SPECIFIC LNCRNAS, WHICH MAY PROVIDE NEW INSIGHTS INTO OUR UNDERSTANDING OF THE ETIOLOGY AND PATHOPHYSIOLOGY OF THE NEURODEGENERATIVE DISEASES MENTIONED ABOVE. 2017 3 330 30 ALPHA-SYNUCLEIN AND MECHANISMS OF EPIGENETIC REGULATION. SYNUCLEINOPATHIES ARE A GROUP OF NEURODEGENERATIVE DISEASES WITH COMMON PATHOLOGICAL LESIONS ASSOCIATED WITH THE EXCESSIVE ACCUMULATION AND ABNORMAL INTRACELLULAR DEPOSITION OF TOXIC SPECIES OF ALPHA-SYNUCLEIN. THE SHARED CLINICAL FEATURES ARE CHRONIC PROGRESSIVE DECLINE OF MOTOR, COGNITIVE, AND BEHAVIORAL FUNCTIONS. THESE DISORDERS INCLUDE PARKINSON'S DISEASE, DEMENTIA WITH LEWY BODY, AND MULTIPLE SYSTEM ATROPHY. VIGOROUS RESEARCH IN THE MECHANISMS OF PATHOLOGY OF THESE ILLNESSES IS CURRENTLY UNDER WAY TO FIND DISEASE-MODIFYING TREATMENT AND MOLECULAR MARKERS FOR EARLY DIAGNOSIS. ALPHA-SYNUCLEIN IS A PRONE-TO-AGGREGATE, SMALL AMYLOIDOGENIC PROTEIN WITH MULTIPLE ROLES IN SYNAPTIC VESICLE TRAFFICKING, NEUROTRANSMITTER RELEASE, AND INTRACELLULAR SIGNALING EVENTS. ITS EXPRESSION IS CONTROLLED BY SEVERAL MECHANISMS, ONE OF WHICH IS EPIGENETIC REGULATION. WHEN TRANSMITTED TO THE NUCLEUS, ALPHA-SYNUCLEIN BINDS TO DNA AND HISTONES AND PARTICIPATES IN EPIGENETIC REGULATORY FUNCTIONS CONTROLLING SPECIFIC GENE TRANSCRIPTION. HERE, WE DISCUSS THE VARIOUS ASPECTS OF ALPHA-SYNUCLEIN INVOLVEMENT IN EPIGENETIC REGULATION IN HEALTH AND DISEASES. 2023 4 6347 26 THE ROLE OF EPIGENETICS IN NEUROINFLAMMATORY-DRIVEN DISEASES. NEURODEGENERATIVE DISORDERS ARE CHARACTERIZED BY THE PROGRESSIVE LOSS OF CENTRAL AND/OR PERIPHERAL NERVOUS SYSTEM NEURONS. WITHIN THIS CONTEXT, NEUROINFLAMMATION COMES UP AS ONE OF THE MAIN FACTORS LINKED TO NEURODEGENERATION PROGRESSION. IN FACT, NEUROINFLAMMATION HAS BEEN RECOGNIZED AS AN OUTSTANDING FACTOR FOR ALZHEIMER'S DISEASE (AD), AMYOTROPHIC LATERAL SCLEROSIS (ALS), PARKINSON'S DISEASE (PD), AND MULTIPLE SCLEROSIS (MS). INTERESTINGLY, NEUROINFLAMMATORY DISEASES ARE CHARACTERIZED BY DRAMATIC CHANGES IN THE EPIGENETIC PROFILE, WHICH MIGHT PROVIDE NOVEL PROGNOSTIC AND THERAPEUTIC FACTORS TOWARDS NEUROINFLAMMATORY TREATMENT. DEEP CHANGES IN DNA AND HISTONE METHYLATION, ALONG WITH HISTONE ACETYLATION AND ALTERED NON-CODING RNA EXPRESSION, HAVE BEEN REPORTED AT THE ONSET OF INFLAMMATORY DISEASES. THE AIM OF THIS WORK IS TO REVIEW THE CURRENT KNOWLEDGE ON THIS FIELD. 2022 5 2858 25 FROM RILUZOLE TO DEXPRAMIPEXOLE VIA SUBSTITUTED-BENZOTHIAZOLE DERIVATIVES FOR AMYOTROPHIC LATERAL SCLEROSIS DISEASE TREATMENT: CASE STUDIES. THE 1,3-BENZOTHIAZOLE (BTZ) RING MAY OFFER A VALID OPTION FOR SCAFFOLD-HOPPING FROM INDOLE DERIVATIVES. SEVERAL BTZS HAVE CLINICALLY RELEVANT ROLES, MAINLY AS CNS MEDICINES AND DIAGNOSTIC AGENTS, WITH RILUZOLE BEING ONE OF THE MOST FAMOUS EXAMPLES. RILUZOLE IS CURRENTLY THE ONLY APPROVED DRUG TO TREAT AMYOTROPHIC LATERAL SCLEROSIS (ALS) BUT ITS EFFICACY IS MARGINAL. SEVERAL CLINICAL STUDIES HAVE DEMONSTRATED ONLY LIMITED IMPROVEMENTS IN SURVIVAL, WITHOUT BENEFITS TO MOTOR FUNCTION IN PATIENTS WITH ALS. DESPITE SIGNIFICANT CLINICAL TRIAL EFFORTS TO UNDERSTAND THE GENETIC, EPIGENETIC, AND MOLECULAR PATHWAYS LINKED TO ALS PATHOPHYSIOLOGY, THERAPEUTIC TRANSLATION HAS REMAINED DISAPPOINTINGLY SLOW, PROBABLY DUE TO THE COMPLEXITY AND THE HETEROGENEITY OF THIS DISEASE. MANY OTHER DRUGS TO TACKLE ALS HAVE BEEN TESTED FOR 20 YEARS WITHOUT ANY SUCCESS. DEXPRAMIPEXOLE IS A BTZ STRUCTURAL ANALOG OF RILUZOLE AND WAS A GREAT HOPE FOR THE TREATMENT OF ALS. IN THIS REVIEW, AS AN INTERESTING CASE STUDY IN THE DEVELOPMENT OF A NEW MEDICINE TO TREAT ALS, WE PRESENT THE STRATEGY OF THE DEVELOPMENT OF DEXPRAMIPEXOLE, WHICH WAS ONE OF THE MOST PROMISING DRUGS AGAINST ALS. 2020 6 1600 32 DNA METHYLATION SIGNATURES OF ALZHEIMER'S DISEASE NEUROPATHOLOGY IN THE CORTEX ARE PRIMARILY DRIVEN BY VARIATION IN NON-NEURONAL CELL-TYPES. ALZHEIMER'S DISEASE (AD) IS A CHRONIC NEURODEGENERATIVE DISEASE CHARACTERIZED BY THE PROGRESSIVE ACCUMULATION OF AMYLOID-BETA AND NEUROFIBRILLARY TANGLES OF TAU IN THE NEOCORTEX. WE PROFILED DNA METHYLATION IN TWO REGIONS OF THE CORTEX FROM 631 DONORS, PERFORMING AN EPIGENOME-WIDE ASSOCIATION STUDY OF MULTIPLE MEASURES OF AD NEUROPATHOLOGY. WE META-ANALYZED OUR RESULTS WITH THOSE FROM PREVIOUS STUDIES OF DNA METHYLATION IN AD CORTEX (TOTAL N = 2013 DONORS), IDENTIFYING 334 CORTICAL DIFFERENTIALLY METHYLATED POSITIONS (DMPS) ASSOCIATED WITH AD PATHOLOGY INCLUDING METHYLOMIC VARIATION AT LOCI NOT PREVIOUSLY IMPLICATED IN DEMENTIA. WE SUBSEQUENTLY PROFILED DNA METHYLATION IN NEUN+ (NEURONAL-ENRICHED), SOX10+ (OLIGODENDROCYTE-ENRICHED) AND NEUN-/SOX10- (MICROGLIA- AND ASTROCYTE-ENRICHED) NUCLEI, FINDING THAT THE MAJORITY OF DMPS IDENTIFIED IN 'BULK' CORTEX TISSUE REFLECT DNA METHYLATION DIFFERENCES OCCURRING IN NON-NEURONAL CELLS. OUR STUDY HIGHLIGHTS THE POWER OF UTILIZING MULTIPLE MEASURES OF NEUROPATHOLOGY TO IDENTIFY EPIGENETIC SIGNATURES OF AD AND THE IMPORTANCE OF CHARACTERIZING DISEASE-ASSOCIATED VARIATION IN PURIFIED CELL-TYPES. 2022 7 3647 36 INCREASED REELIN PROMOTER METHYLATION IS ASSOCIATED WITH GRANULE CELL DISPERSION IN HUMAN TEMPORAL LOBE EPILEPSY. MESIAL TEMPORAL SCLEROSIS (MTS) IS THE MOST COMMON LESION IN CHRONIC, INTRACTABLE TEMPORAL LOBE EPILEPSIES (TLE) AND CHARACTERIZED BY SEGMENTAL NEURONAL CELL LOSS IN MAJOR HIPPOCAMPAL SEGMENTS. ANOTHER HISTOPATHOLOGICAL HALLMARK INCLUDES GRANULE CELL DISPERSION (GCD), AN ARCHITECTURAL DISTURBANCE OF THE DENTATE GYRUS ENCOUNTERED IN APPROXIMATELY 50% OF PATIENTS WITH MESIAL TEMPORAL SCLEROSIS. REELIN, WHICH PLAYS A KEY ROLE DURING HIPPOCAMPAL DEVELOPMENT AND MAINTENANCE OF LAMINAR ORGANIZATION, IS SYNTHESIZED AND RELEASED BY CAJAL-RETZIUS CELLS OF THE DENTATE MOLECULAR LAYER, AND PREVIOUS STUDIES HAVE SHOWN THAT REELIN TRANSCRIPT LEVELS ARE DOWNREGULATED IN HUMAN TEMPORAL LOBE EPILEPSIES SPECIMENS. TO INVESTIGATE WHETHER EPIGENETIC SILENCING BY REELIN PROMOTER METHYLATION MAY BE AN UNDERLYING PATHOGENETIC MECHANISM OF GCD, DNA WAS HARVESTED FROM 3 MICRODISSECTED HIPPOCAMPAL SUBREGIONS (I.E. MOLECULAR AND GRANULE CELL LAYERS OF THE DENTATE GYRUS AND PRESUBICULUM) FROM 8 MTS SPECIMENS WITH GCD, 5 TLE SAMPLES WITHOUT GCD, AND 3 AUTOPSY CONTROLS. PROMOTER METHYLATION WAS ANALYZED AFTER BISULFITE TREATMENT, CLONING, AND DIRECT SEQUENCING; IMMUNOHISTOCHEMISTRY WAS PERFORMED TO IDENTIFY CAJAL-RETZIUS CELLS. REELIN PROMOTER METHYLATION WAS FOUND TO BE GREATER IN TLE SPECIMENS THAN IN CONTROLS; PROMOTER METHYLATION CORRELATED WITH GCD AMONG TLE SPECIMENS (P < 0.0002). NO OTHER CLINICAL OR HISTOPATHOLOGICAL PARAMETER (I.E. SEX, AGE, SEIZURE DURATION, MEDICATION OR EXTENT, OF MTS) CORRELATED WITH PROMOTER METHYLATION. THESE DATA SUPPORT A COMPROMISED REELIN-SIGNALING PATHWAY AND IDENTIFY PROMOTER METHYLATION AS AN EPIGENETIC MECHANISM IN THE PATHOGENESIS OF TLE. 2009 8 5580 27 ROLE OF NEUROTOXICANTS IN THE PATHOGENESIS OF ALZHEIMER'S DISEASE: A MECHANISTIC INSIGHT. ALZHEIMER'S DISEASE (AD) IS THE MOST CONSPICUOUS CHRONIC NEURODEGENERATIVE SYNDROME, WHICH HAS BECOME A SIGNIFICANT CHALLENGE FOR THE GLOBAL HEALTHCARE SYSTEM. MULTIPLE STUDIES HAVE CORROBORATED A CLEAR ASSOCIATION OF NEUROTOXICANTS WITH AD PATHOGENICITY, SUCH AS AMYLOID BETA (ABETA) PROTEINS AND NEUROFIBRILLARY TANGLES (NFTS), SIGNALLING PATHWAY MODIFICATIONS, CELLULAR STRESS, COGNITIVE DYSFUNCTIONS, NEURONAL APOPTOSIS, NEUROINFLAMMATION, EPIGENETIC MODIFICATION, AND SO ON. THIS REVIEW, THEREFORE, AIMED TO ADDRESS SEVERAL ESSENTIAL MECHANISMS AND SIGNALLING CASCADES, INCLUDING WNT (WINGLESS AND INT.) SIGNALLING PATHWAY, AUTOPHAGY, MAMMALIAN TARGET OF RAPAMYCIN (MTOR), PROTEIN KINASE C (PKC) SIGNALLING CASCADES, CELLULAR REDOX STATUS, ENERGY METABOLISM, GLUTAMATERGIC NEUROTRANSMISSIONS, IMMUNE CELL STIMULATIONS (E.G. MICROGLIA, ASTROCYTES) AS WELL AS AN AMYLOID PRECURSOR PROTEIN (APP), PRESENILIN-1 (PSEN1), PRESENILIN-2 (PSEN2) AND OTHER AD-RELATED GENE EXPRESSIONS THAT HAVE BEEN PRETENTIOUS AND MODULATED BY THE VARIOUS NEUROTOXICANTS. THIS REVIEW CONCLUDED THAT NEUROTOXICANTS PLAY A MOMENTOUS ROLE IN DEVELOPING AD THROUGH MODULATING VARIOUS SIGNALLING CASCADES. NEVERTHELESS, COMPREHENSION OF THIS RISK AGENT-INDUCED NEUROTOXICITY IS FAR TOO LITTLE. MORE IN-DEPTH EPIDEMIOLOGICAL AND SYSTEMATIC INVESTIGATIONS ARE NEEDED TO UNDERSTAND THE POTENTIAL MECHANISMS BETTER TO ADDRESS THESE NEUROTOXICANTS AND IMPROVE APPROACHES TO THEIR RISK EXPOSURE THAT AID IN AD PATHOGENESIS.KEY MESSAGESINEVITABLE CASCADE MECHANISMS OF HOW ALZHEIMER'S DISEASE-RELATED (AD-RELATED) GENE EXPRESSIONS ARE MODULATED BY NEUROTOXICANTS HAVE BEEN DISCUSSED.INVOLVEMENT OF THE NEUROTOXICANTS-INDUCED PATHWAYS CAUSED AN EXTENDED RISK OF AD IS EXPLICITED.INTEGRATION OF CELL CULTURE, ANIMALS AND POPULATION-BASED ANALYSIS ON THE CLINICAL SEVERITY OF AD IS ADDRESSED. 2021 9 6904 29 [THE ROLE OF ALUMINUM AND LEAD IN THE DEVELOPMENT OF ALZHEIMER'S AND PARKINSON'S DISEASES]. THE ARTICLE SUMMARIZES THE DATA AVAILABLE IN THE LITERATURE ON THE TOXIC EFFECTS OF ALUMINUM AND LEAD ON THE HUMAN BRAIN AND ASSESSES THE RELATIONSHIP OF THESE EFFECTS TO THE ETIOPATHOGENESIS OF THE MOST COMMON NEURODEGENERATIVE DISEASES, SUCH AS ALZHEIMER'S AND PARKINSON'S DISEASES. THE ACCUMULATION OF IONS OF THESE METALS IN THE BRAIN STRUCTURES LEADS TO CHRONIC INTOXICATION THAT IS MANIFESTED BY THE MORPHOLOGICAL SIGNS THAT ARE TYPICAL FOR ALZHEIMER'S DISEASE, SUCH AS DEPOSITS OF BETA-AMYLOID AND TAU-PROTEIN MAINLY IN THE FRONTAL AND TEMPORAL REGIONS OF THE CORTEX, AND FOR PARKINSON'S DISEASE, SUCH AS DEGENERATION OF DOPAMINE NEURONS IN THE SUBSTANTIA NIGRA AND THEIR ACCUMULATION OF ALPHA-SYNUCLEIN. THE MOST LIKELY FORMS OF PARTICIPATION OF ALUMINUM AND LEAD IONS IN THE MECHANISMS OF NEURODEGENERATION ARE THE REPLACEMENT OF BIVALENT METAL IONS NECESSARY FOR BRAIN FUNCTIONING, OXIDATIVE STRESS INITIATION, EPIGENETIC MODIFICATIONS OF HISTONES, AND INCREASED EXPRESSION OF NONCODING RIBONUCLEIC ACIDS. 2021 10 1299 32 DECREASED REELIN EXPRESSION IN THE LEFT PREFRONTAL CORTEX (BA9) IN CHRONIC SCHIZOPHRENIA PATIENTS. BACKGROUND: REELIN IS UNDER EPIGENETIC CONTROL AND HAS BEEN REPORTED TO BE DECREASED IN CORTICAL REGIONS IN SCHIZOPHRENIA. METHODS: TO ESTABLISH IF EXPRESSION OF REELIN IS ALTERED IN SPECIFIC CORTICAL, HIPPOCAMPAL OR THALAMIC REGIONS OF SCHIZOPHRENIA PATIENTS, WE MEASURED GENE EXPRESSION OF REELIN IN A POSTMORTEM STUDY OF ELDERLY PATIENTS WITH SCHIZOPHRENIA AND NON-AFFECTED CONTROLS IN BOTH HEMISPHERES DIFFERENTIATING BETWEEN GRAY AND WHITE MATTER. WE COMPARED CEREBRAL POSTMORTEM SAMPLES (DORSOLATERAL PREFRONTAL CORTEX BA9 AND BA46, SUPERIOR TEMPORAL CORTEX BA22, ENTORHINAL CORTEX BA28, SENSORIC CORTEX BA1-3, HIPPOCAMPUS, CA4, MEDIODORSAL NUCLEUS OF THE THALAMUS) FROM 12 SCHIZOPHRENIA PATIENTS WITH 13 NORMAL SUBJECTS INVESTIGATING GENE EXPRESSION OF REELIN IN THE GRAY AND WHITE MATTER OF BOTH HEMISPHERES BY IN SITU-HYBRIDIZATION. RESULTS: THE LEFT PREFRONTAL AREA (BA9) OF SCHIZOPHRENIA PATIENTS REVEALED A DECREASED EXPRESSION OF REELIN-MRNA OF 29.1% IN THE WHITE (P = 0.022) AND 13.6% IN THE GRAY MATTER (P = 0.007) COMPARED TO THE CONTROL GROUP. NONE OF THE OTHER REGIONS EXAMINED SHOWED ANY STATISTICALLY SIGNIFICANT DIFFERENCES. CONCLUSION: SINCE REELIN IS RESPONSIBLE FOR MIGRATION AND SYNAPSE FORMATION, THE DECREASED GENE EXPRESSION OF REELIN IN THE LEFT PREFRONTAL AREA OF SCHIZOPHRENIA PATIENTS POINTS TO NEURODEVELOPMENTAL DEFICITS IN NEURONAL MIGRATION AND SYNAPTIC PLASTICITY. HOWEVER, OUR STUDY GROUP WAS SMALL, AND RESULTS SHOULD BE VERIFIED USING LARGER SAMPLES. 2012 11 4638 34 NEURON-SPECIFIC METHYLOME ANALYSIS REVEALS EPIGENETIC REGULATION AND TAU-RELATED DYSFUNCTION OF BRCA1 IN ALZHEIMER'S DISEASE. ALZHEIMER'S DISEASE (AD) IS A CHRONIC NEURODEGENERATIVE DISEASE CHARACTERIZED BY PATHOLOGY OF ACCUMULATED AMYLOID BETA (ABETA) AND PHOSPHORYLATED TAU PROTEINS IN THE BRAIN. POSTMORTEM DEGRADATION AND CELLULAR COMPLEXITY WITHIN THE BRAIN HAVE LIMITED APPROACHES TO MOLECULARLY DEFINE THE CAUSAL RELATIONSHIP BETWEEN PATHOLOGICAL FEATURES AND NEURONAL DYSFUNCTION IN AD. TO OVERCOME THESE LIMITATIONS, WE ANALYZED THE NEURON-SPECIFIC DNA METHYLOME OF POSTMORTEM BRAIN SAMPLES FROM AD PATIENTS, WHICH ALLOWED DIFFERENTIALLY HYPOMETHYLATED REGION OF THE BRCA1 PROMOTER TO BE IDENTIFIED. EXPRESSION OF BRCA1 WAS SIGNIFICANTLY UP-REGULATED IN AD BRAINS, CONSISTENT WITH ITS HYPOMETHYLATION. BRCA1 PROTEIN LEVELS WERE ALSO ELEVATED IN RESPONSE TO DNA DAMAGE INDUCED BY ABETA. BRCA1 BECAME MISLOCALIZED TO THE CYTOPLASM AND HIGHLY INSOLUBLE IN A TAU-DEPENDENT MANNER, RESULTING IN DNA FRAGMENTATION IN BOTH IN VITRO CELLULAR AND IN VIVO MOUSE MODELS. BRCA1 DYSFUNCTION UNDER ABETA BURDEN IS CONSISTENT WITH CONCOMITANT DETERIORATION OF GENOMIC INTEGRITY AND SYNAPTIC PLASTICITY. THE BRCA1 PROMOTER REGION OF AD MODEL MICE BRAIN WAS SIMILARLY HYPOMETHYLATED, INDICATING AN EPIGENETIC MECHANISM UNDERLYING BRCA1 REGULATION IN AD. OUR RESULTS SUGGEST DETERIORATION OF DNA INTEGRITY AS A CENTRAL CONTRIBUTING FACTOR IN AD PATHOGENESIS. MOREOVER, THESE DATA DEMONSTRATE THE TECHNICAL FEASIBILITY OF USING NEURON-SPECIFIC DNA METHYLOME ANALYSIS TO FACILITATE DISCOVERY OF ETIOLOGICAL CANDIDATES IN SPORADIC NEURODEGENERATIVE DISEASES. 2017 12 6153 27 THE FUNCTION OF THE METALS IN REGULATING EPIGENETICS DURING PARKINSON'S DISEASE. PARKINSON'S MEANS PARKINSON'S DISEASE, A CHRONIC DEGENERATIVE DISEASE OF CENTRAL NERVOUS SYSTEM. THE MAIN AREA WHICH IS AFFECTED BY THIS DISEASE IS MOTOR SYSTEM. SINCE IT FIRSTLY FOUNDED BY JAMES PARKINSON IN HIS 1817 PUBLICATION, NOWADAYS, PEOPLE STILL HAVE LOTS OF QUESTIONS ABOUT THIS DISEASE. THIS REVIEW MAINLY SUMMARIZES THE EPIGENETICS OF PARKINSON'S. DNA METHYLATION IS ONE OF THE EPIGENETIC MECHANISMS OF PARKINSON'S. DURING THE DEVELOPMENT OF DISEASE, GLOBAL HYPOMETHYLATION, AND HYPERMETHYLATION HAPPEN IN DIFFERENT AREAS OF PATIENTS. ANOTHER EPIGENETIC MECHANISM IS HISTONE MODIFICATION. PEOPLE BELIEVE THAT SOME METALS CAN INDUCE PARKINSON'S DISEASE BY MODULATING EPIGENETIC MECHANISMS. THIS REVIEW SUMMARIZES THE RELATIONSHIPS BETWEEN DIFFERENT METALS AND PARKINSON'S DISEASE. HOWEVER, THE SPECIFIC ROLES OF MOST METALS IN EPIGENETICS ARE STILL UNKNOWN, WHICH NEED FURTHER RESEARCH. 2020 13 1425 39 DIFFERENTIAL DNA METHYLATION PROFILES OF CODING AND NON-CODING GENES DEFINE HIPPOCAMPAL SCLEROSIS IN HUMAN TEMPORAL LOBE EPILEPSY. TEMPORAL LOBE EPILEPSY IS ASSOCIATED WITH LARGE-SCALE, WIDE-RANGING CHANGES IN GENE EXPRESSION IN THE HIPPOCAMPUS. EPIGENETIC CHANGES TO DNA ARE ATTRACTIVE MECHANISMS TO EXPLAIN THE SUSTAINED HYPEREXCITABILITY OF CHRONIC EPILEPSY. HERE, THROUGH METHYLATION ANALYSIS OF ALL ANNOTATED C-PHOSPHATE-G ISLANDS AND PROMOTER REGIONS IN THE HUMAN GENOME, WE REPORT A PILOT STUDY OF THE METHYLATION PROFILES OF TEMPORAL LOBE EPILEPSY WITH OR WITHOUT HIPPOCAMPAL SCLEROSIS. FURTHERMORE, BY COMPARATIVE ANALYSIS OF EXPRESSION AND PROMOTER METHYLATION, WE IDENTIFY METHYLATION SENSITIVE NON-CODING RNA IN HUMAN TEMPORAL LOBE EPILEPSY. A TOTAL OF 146 PROTEIN-CODING GENES EXHIBITED ALTERED DNA METHYLATION IN TEMPORAL LOBE EPILEPSY HIPPOCAMPUS (N = 9) WHEN COMPARED TO CONTROL (N = 5), WITH 81.5% OF THE PROMOTERS OF THESE GENES DISPLAYING HYPERMETHYLATION. UNIQUE METHYLATION PROFILES WERE EVIDENT IN TEMPORAL LOBE EPILEPSY WITH OR WITHOUT HIPPOCAMPAL SCLEROSIS, IN ADDITION TO A COMMON METHYLATION PROFILE REGARDLESS OF PATHOLOGY GRADE. GENE ONTOLOGY TERMS ASSOCIATED WITH DEVELOPMENT, NEURON REMODELLING AND NEURON MATURATION WERE OVER-REPRESENTED IN THE METHYLATION PROFILE OF WATSON GRADE 1 SAMPLES (MILD HIPPOCAMPAL SCLEROSIS). IN ADDITION TO GENES ASSOCIATED WITH NEURONAL, NEUROTRANSMITTER/SYNAPTIC TRANSMISSION AND CELL DEATH FUNCTIONS, DIFFERENTIAL HYPERMETHYLATION OF GENES ASSOCIATED WITH TRANSCRIPTIONAL REGULATION WAS EVIDENT IN TEMPORAL LOBE EPILEPSY, BUT OVERALL FEW GENES PREVIOUSLY ASSOCIATED WITH EPILEPSY WERE AMONG THE DIFFERENTIALLY METHYLATED. FINALLY, A PANEL OF 13, METHYLATION-SENSITIVE MICRORNA WERE IDENTIFIED IN TEMPORAL LOBE EPILEPSY INCLUDING MIR27A, MIR-193A-5P (MIR193A) AND MIR-876-3P (MIR876), AND THE DIFFERENTIAL METHYLATION OF LONG NON-CODING RNA DOCUMENTED FOR THE FIRST TIME. THE PRESENT STUDY THEREFORE REPORTS SELECT, GENOME-WIDE DNA METHYLATION CHANGES IN HUMAN TEMPORAL LOBE EPILEPSY THAT MAY CONTRIBUTE TO THE MOLECULAR ARCHITECTURE OF THE EPILEPTIC BRAIN. 2015 14 5583 22 ROLE OF NON-CODING RNAS IN NON-AGING-RELATED NEUROLOGICAL DISORDERS. PROTEIN CODING SEQUENCES REPRESENT ONLY 2% OF THE HUMAN GENOME. RECENT ADVANCES HAVE DEMONSTRATED THAT A SIGNIFICANT PORTION OF THE GENOME IS ACTIVELY TRANSCRIBED AS NON-CODING RNA MOLECULES. THESE NON-CODING RNAS ARE EMERGING AS KEY PLAYERS IN THE REGULATION OF BIOLOGICAL PROCESSES, AND ACT AS "FINE-TUNERS" OF GENE EXPRESSION. NEUROLOGICAL DISORDERS ARE CAUSED BY A WIDE RANGE OF GENETIC MUTATIONS, EPIGENETIC AND ENVIRONMENTAL FACTORS, AND THE EXACT PATHOPHYSIOLOGY OF MANY OF THESE CONDITIONS IS STILL UNKNOWN. IT IS CURRENTLY RECOGNIZED THAT DYSREGULATIONS IN THE EXPRESSION OF NON-CODING RNAS ARE PRESENT IN MANY NEUROLOGICAL DISORDERS AND MAY BE RELEVANT IN THE MECHANISMS LEADING TO DISEASE. IN ADDITION, CIRCULATING NON-CODING RNAS ARE EMERGING AS POTENTIAL BIOMARKERS WITH GREAT POTENTIAL IMPACT IN CLINICAL PRACTICE. IN THIS REVIEW, WE DISCUSS MAINLY THE ROLE OF MICRORNAS AND LONG NON-CODING RNAS IN SEVERAL NEUROLOGICAL DISORDERS, SUCH AS EPILEPSY, HUNTINGTON DISEASE, FRAGILE X-ASSOCIATED ATAXIA, SPINOCEREBELLAR ATAXIAS, AMYOTROPHIC LATERAL SCLEROSIS (ALS), AND PAIN. IN ADDITION, WE GIVE INFORMATION ABOUT THE CONDITIONS WHERE MICRORNAS HAVE DEMONSTRATED TO BE POTENTIAL BIOMARKERS SUCH AS IN EPILEPSY, PAIN, AND ALS. 2018 15 6227 29 THE LINK OF ORGANOPHOSPHORUS PESTICIDES WITH NEURODEGENERATIVE AND NEURODEVELOPMENTAL DISEASES BASED ON EVIDENCE AND MECHANISMS. ORGANOPHOSPHORUS (OP) COMPOUNDS HAVE BEEN KNOWN AS THE MOST WIDELY USED PESTICIDES DURING THE PAST HALF CENTURY AND THERE HAVE BEEN A HUGE BODY OF LITERATURE REGARDING THEIR ASSOCIATION WITH HUMAN CHRONIC DISEASES. NEURODEGENERATIVE AND NEURODEVELOPMENTAL DISORDERS INCLUDING ALZHEIMER, PARKINSON, AMYOTROPHIC LATERAL SCLEROSIS (ALS), ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD), AND AUTISM ARE AMONG THE AFFLICTING NEUROLOGICAL DISEASES WHICH OVERSHADOW HUMAN LIFE AND THEIR HIGHER RISK IN RELATION TO OP EXPOSURES HAVE BEEN UNCOVERED BY EPIDEMIOLOGICAL STUDIES. IN ADDITION, EXPERIMENTAL STUDIES EXPLORING THE UNDERLYING MECHANISMS HAVE PROVIDED SOME EVIDENCE FOR INVOLVEMENT OF CHOLINERGIC DEFICIT, OXIDATIVE STRESS, NEURO-INFLAMMATION, AND EPIGENETIC MODIFICATIONS AS THE PROCESSES WHICH ARE COMMON IN THE TOXICITY OF THE OP AND PATHOPHYSIOLOGY OF THE MENTIONED DISEASES. IN ADDITION, GENETIC MUTATIONS AND POLYMORPHISMS OF DIFFERENT VARIANTS OF SOME GENES LIKE PARAOXONASE HAVE BEEN SHOWN TO BE IMPLICATED IN BOTH SUSCEPTIBILITY TO OPS TOXICITY AND NEUROLOGICAL DISEASES. IN THIS ARTICLE, WE REVIEWED THE EPIDEMIOLOGICAL AS WELL AS EXPERIMENTAL STUDIES EVIDENCING THE ASSOCIATION OF EXPOSURE TO OPS AND INCIDENCE OF NEURODEGENERATIVE AND NEURODEVELOPMENTAL DISEASES. 2018 16 4130 27 MECHANISMS OF FERROPTOSIS AND EMERGING LINKS TO THE PATHOLOGY OF NEURODEGENERATIVE DISEASES. NEURODEGENERATIVE DISEASES ARE A DIVERSE CLASS OF DISEASES ATTRIBUTED TO CHRONIC PROGRESSIVE NEURONAL DEGENERATION AND SYNAPTIC LOSS IN THE BRAIN AND/OR SPINAL CORD, INCLUDING ALZHEIMER'S DISEASE, PARKINSON'S DISEASE, HUNTINGTON'S DISEASE, AMYOTROPHIC LATERAL SCLEROSIS AND MULTIPLE SCLEROSIS. THE PATHOGENESIS OF NEURODEGENERATIVE DISEASES IS COMPLEX AND DIVERSE, OFTEN INVOLVING MITOCHONDRIAL DYSFUNCTION, NEUROINFLAMMATION, AND EPIGENETIC CHANGES. HOWEVER, THE PATHOGENESIS OF NEURODEGENERATIVE DISEASES HAS NOT BEEN FULLY ELUCIDATED. RECENTLY, ACCUMULATING EVIDENCE REVEALED THAT FERROPTOSIS, A NEWLY DISCOVERED IRON-DEPENDENT AND LIPID PEROXIDATION-DRIVEN TYPE OF PROGRAMMED CELL DEATH, PROVIDES ANOTHER EXPLANATION FOR THE OCCURRENCE AND PROGRESSION OF NEURODEGENERATIVE DISEASES. HERE, WE PROVIDE AN OVERVIEW OF THE PROCESS AND REGULATION MECHANISMS OF FERROPTOSIS, AND SUMMARIZE CURRENT RESEARCH PROGRESSES THAT SUPPORT THE CONTRIBUTION OF FERROPTOSIS TO THE PATHOGENESIS OF NEURODEGENERATIVE DISEASES. A COMPREHENSIVE UNDERSTANDING OF THE EMERGING ROLES OF FERROPTOSIS IN NEURODEGENERATIVE DISEASES WILL SHED LIGHT ON THE DEVELOPMENT OF NOVEL THERAPEUTIC TECHNOLOGIES AND STRATEGIES FOR SLOWING DOWN THE PROGRESSION OF THESE DISEASES. 2022 17 2130 28 EPIGENETIC INACTIVATION OF THE AUTOPHAGY-LYSOSOMAL SYSTEM IN APPENDIX IN PARKINSON'S DISEASE. THE GASTROINTESTINAL TRACT MAY BE A SITE OF ORIGIN FOR ALPHA-SYNUCLEIN PATHOLOGY IN IDIOPATHIC PARKINSON'S DISEASE (PD). DISRUPTION OF THE AUTOPHAGY-LYSOSOME PATHWAY (ALP) MAY CONTRIBUTE TO ALPHA-SYNUCLEIN AGGREGATION. HERE WE EXAMINED EPIGENETIC ALTERATIONS IN THE ALP IN THE APPENDIX BY DEEP SEQUENCING DNA METHYLATION AT 521 ALP GENES. WE IDENTIFIED ABERRANT METHYLATION AT 928 CYTOSINES AFFECTING 326 ALP GENES IN THE APPENDIX OF INDIVIDUALS WITH PD AND WIDESPREAD HYPERMETHYLATION THAT IS ALSO SEEN IN THE BRAIN OF INDIVIDUALS WITH PD. IN MICE, WE FIND THAT DNA METHYLATION CHANGES AT ALP GENES INDUCED BY CHRONIC GUT INFLAMMATION ARE GREATLY EXACERBATED BY ALPHA-SYNUCLEIN PATHOLOGY. DNA METHYLATION CHANGES AT ALP GENES INDUCED BY SYNUCLEINOPATHY ARE ASSOCIATED WITH THE ALP ABNORMALITIES OBSERVED IN THE APPENDIX OF INDIVIDUALS WITH PD SPECIFICALLY INVOLVING LYSOSOMAL GENES. OUR WORK IDENTIFIES EPIGENETIC DYSREGULATION OF THE ALP WHICH MAY SUGGEST A POTENTIAL MECHANISM FOR ACCUMULATION OF ALPHA-SYNUCLEIN PATHOLOGY IN IDIOPATHIC PD. 2021 18 5143 28 POTENTIAL ROLE OF EPIGENETIC MECHANISM IN MANGANESE INDUCED NEUROTOXICITY. MANGANESE IS A VITAL NUTRIENT AND IS MAINTAINED AT AN OPTIMAL LEVEL (2.5-5 MG/DAY) IN HUMAN BODY. CHRONIC EXPOSURE TO MANGANESE IS ASSOCIATED WITH NEUROTOXICITY AND CORRELATED WITH THE DEVELOPMENT OF VARIOUS NEUROLOGICAL DISORDERS SUCH AS PARKINSON'S DISEASE. OXIDATIVE STRESS MEDIATED APOPTOTIC CELL DEATH HAS BEEN WELL ESTABLISHED MECHANISM IN MANGANESE INDUCED TOXICITY. OXIDATIVE STRESS HAS A POTENTIAL TO ALTER THE EPIGENETIC MECHANISM OF GENE REGULATION. EPIGENETIC INSIGHT OF MANGANESE NEUROTOXICITY IN CONTEXT OF ITS CORRELATION WITH THE DEVELOPMENT OF PARKINSONISM IS POORLY UNDERSTOOD. PARKINSON'S DISEASE IS CHARACTERIZED BY THE ALPHA-SYNUCLEIN AGGREGATION IN THE FORM OF LEWY BODIES IN NEURONAL CELLS. RECENT FINDINGS ILLUSTRATE THAT MANGANESE CAN CAUSE OVEREXPRESSION OF ALPHA-SYNUCLEIN. ALPHA-SYNUCLEIN ACTS EPIGENETICALLY VIA INTERACTION WITH HISTONE PROTEINS IN REGULATING APOPTOSIS. ALPHA-SYNUCLEIN ALSO CAUSES GLOBAL DNA HYPOMETHYLATION THROUGH SEQUESTRATION OF DNA METHYLTRANSFERASE IN CYTOPLASM. AN INDIVIDUAL GENETIC DIFFERENCE MAY ALSO HAVE AN INFLUENCE ON EPIGENETIC SUSCEPTIBILITY TO MANGANESE NEUROTOXICITY AND THE DEVELOPMENT OF PARKINSON'S DISEASE. THIS REVIEW PRESENTS THE CURRENT STATE OF FINDINGS IN RELATION TO ROLE OF EPIGENETIC MECHANISM IN MANGANESE INDUCED NEUROTOXICITY, WITH A SPECIAL EMPHASIS ON THE DEVELOPMENT OF PARKINSON'S DISEASE. 2016 19 2010 34 EPIGENETIC BASIS OF LEAD-INDUCED NEUROLOGICAL DISORDERS. ENVIRONMENTAL LEAD (PB) EXPOSURE IS CLOSELY ASSOCIATED WITH PATHOGENESIS OF A RANGE OF NEUROLOGICAL DISORDERS, INCLUDING ALZHEIMER'S DISEASE (AD), PARKINSON'S DISEASE (PD), AMYOTROPHIC LATERAL SCLEROSIS (ALS), ATTENTION DEFICIT/HYPERACTIVITY DISORDER (ADHD), ETC. EPIGENETIC MACHINERY MODULATES NEURAL DEVELOPMENT AND ACTIVITIES, WHILE FAULTY EPIGENETIC REGULATION CONTRIBUTES TO THE DIVERSE FORMS OF CNS (CENTRAL NERVOUS SYSTEM) ABNORMALITIES AND DISEASES. AS A POTENT EPIGENETIC MODIFIER, LEAD IS THOUGHT TO CAUSE NEUROLOGICAL DISORDERS THROUGH MODULATING EPIGENETIC MECHANISMS. SPECIFICALLY, INCREASING EVIDENCE LINKED ABERRANT DNA METHYLATIONS, HISTONE MODIFICATIONS AS WELL AS NCRNAS (NON-CODING RNAS) WITH AD CASES, AMONG WHICH CIRCRNA (CIRCULAR RNA) STANDS OUT AS A NEW AND PROMISING FIELD FOR ASSOCIATION STUDIES. IN 23-YEAR-OLD PRIMATES WITH DEVELOPMENTAL LEAD TREATMENT, ZAWIA GROUP DISCOVERED A VARIETY OF EPIGENETIC CHANGES RELATING TO AD PATHOGENESIS. THIS IS A DIRECT EVIDENCE IMPLICATING EPIGENETIC BASIS IN LEAD-INDUCED AD ANIMALS WITH AN ENTIRE LIFESPAN. ADDITIONALLY, SOME EPIGENETIC MOLECULES ASSOCIATED WITH AD ETIOLOGY WERE ALSO KNOWN TO RESPOND TO CHRONIC LEAD EXPOSURE IN COMPARABLE DISEASE MODELS, INDICATING POTENTIALLY INTERLACED MECHANISMS WITH RESPECT TO THE STUDIED NEUROTOXIC AND PATHOLOGICAL EVENTS. OF NOTE, EPIGENETIC MOLECULES ACTED VIA GLOBALLY OR SELECTIVELY INFLUENCING THE EXPRESSION OF DISEASE-RELATED GENES. COMPARED TO AD, THE ASSOCIATION OF LEAD EXPOSURE WITH OTHER NEUROLOGICAL DISORDERS WERE PRIMARILY SUPPORTED BY EPIDEMIOLOGICAL SURVEY, WITH FEWER REPORTS CONNECTING EPIGENETIC REGULATORS WITH LEAD-INDUCED PATHOGENESIS. SOME PHARMACEUTICALS, SUCH AS HDAC (HISTONE DEACETYLASE) INHIBITORS AND DNA METHYLATION INHIBITORS, WERE DEVELOPED TO DEAL WITH CNS DISEASE BY TARGETING EPIGENETIC COMPONENTS. STILL, UNDERSTANDINGS ARE INSUFFICIENT REGARDING THE CAUSE-CONSEQUENCE RELATIONS OF EPIGENETIC FACTORS AND NEUROLOGICAL ILLNESS. THEREFORE, CLEAR EVIDENCE SHOULD BE PROVIDED IN FUTURE INVESTIGATIONS TO ADDRESS DETAILED ROLES OF NOVEL EPIGENETIC FACTORS IN LEAD-INDUCED NEUROLOGICAL DISORDERS, AND EFFORTS OF DEVELOPING SPECIFIC EPIGENETIC THERAPEUTICS SHOULD BE APPRAISED. 2020 20 1727 32 DYSREGULATION OF LONG NON-CODING RNAS IN MOUSE MODELS OF LOCALIZATION-RELATED EPILEPSY. GENOME-WIDE PROFILING HAS REVEALED THAT EUKARYOTIC GENOMES ARE TRANSCRIBED INTO NUMEROUS NON-CODING RNAS. IN PARTICULAR, LONG NON-CODING RNAS (LNCRNAS) HAVE BEEN IMPLICATED IN VARIOUS HUMAN DISEASES DUE TO THEIR BIOCHEMICAL AND FUNCTIONAL DIVERSITY. EPILEPTIC DISORDERS HAVE BEEN CHARACTERIZED BY DYSREGULATION OF EPIGENETIC REGULATORY MECHANISMS, AND RECENT STUDIES HAVE IDENTIFIED SEVERAL LNCRNAS INVOLVED IN NEURAL DEVELOPMENT AND NETWORK FUNCTION. HOWEVER, COMPREHENSIVE PROFILING OF LNCRNAS IMPLICATED IN CHRONIC EPILEPSY HAS BEEN LACKING. IN THIS STUDY, MICROARRAY ANALYSIS WAS PERFORMED TO OBTAIN THE EXPRESSION PROFILE OF LNCRNAS DYSREGULATED IN PILOCARPINE AND KAINATE MODELS, TWO MODELS OF TEMPORAL LOBE EPILEPSY COMMONLY USED FOR STUDYING EPILEPTIC MECHANISMS. TOTAL OF 4622 LNCRNAS WERE ANALYZED: 384 LNCRNAS WERE SIGNIFICANTLY DYSREGULATED IN PILOCARPINE MODEL, AND 279 LNCRNAS WERE SIGNIFICANTLY DYSREGULATED IN KAINATE MODEL COMPARED WITH CONTROL MICE (>/=3.0-FOLD, P < 0.05). AMONG THESE, 54 AND 14 LNCRNAS, RESPECTIVELY, HAD ADJACENT PROTEIN-CODING GENES WHOSE EXPRESSIONS WERE ALSO SIGNIFICANTLY DYSREGULATED (>/=2.0-FOLD, P < 0.05). MAJORITY OF THESE PAIRS OF LNCRNAS AND ADJACENT GENES SHARED THE SAME DIRECTION OF DYSREGULATION. FOR THE SELECTED ADJACENT GENE-LNCRNA PAIRS, SIGNIFICANT GENE ONTOLOGY TERMS WERE EMBRYONIC APPENDAGE MORPHOGENESIS AND NEURON DIFFERENTIATION. THIS WAS THE FIRST STUDY TO COMPREHENSIVELY IDENTIFY DYSREGULATED LNCRNAS IN TWO DIFFERENT MODELS OF CHRONIC EPILEPSY AND WILL LIKELY PROVIDE A NOVEL INSIGHT INTO DEVELOPING LNCRNA THERAPEUTICS. 2015