1 1459 149 DISORDERED APP METABOLISM AND NEUROVASCULATURE IN TRAUMA AND AGING: COMBINED RISKS FOR CHRONIC NEURODEGENERATIVE DISORDERS. TRAUMATIC BRAIN INJURY (TBI), ADVANCED AGE, AND CEREBRAL VASCULAR DISEASE ARE FACTORS CONFERRING INCREASED RISK FOR LATE ONSET ALZHEIMER'S DISEASE (AD). THESE CONDITIONS ARE ALSO RELATED PATHOLOGICALLY THROUGH MULTIPLE INTERACTING MECHANISMS. THE HALLMARK PATHOLOGY OF AD CONSISTS OF PATHOLOGICAL AGGREGATES OF AMYLOID-BETA (ABETA) PEPTIDES AND TAU PROTEINS. THESE MOLECULES ARE ALSO INVOLVED IN NEUROPATHOLOGY OF SEVERAL OTHER CHRONIC NEURODEGENERATIVE DISEASES, AND ARE UNDER INTENSE INVESTIGATION IN THE AFTERMATH OF TBI AS POTENTIAL CONTRIBUTORS TO THE RISK FOR DEVELOPING AD AND CHRONIC TRAUMATIC ENCEPHALOPATHY (CTE). THE PATHOLOGY OF TBI IS COMPLEX AND DEPENDENT ON INJURY SEVERITY, AGE-AT-INJURY, AND LENGTH OF TIME BETWEEN INJURY AND NEUROPATHOLOGICAL EVALUATION. IN ADDITION, THE MECHANISMS INFLUENCING PATHOLOGY AND RECOVERY AFTER TBI LIKELY INVOLVE GENETIC/EPIGENETIC FACTORS AS WELL AS ADDITIONAL DISORDERS OR COMORBID STATES RELATED TO AGE AND CENTRAL AND PERIPHERAL VASCULAR HEALTH. IN THIS REGARD, DYSFUNCTION OF THE AGING NEUROVASCULAR SYSTEM COULD BE AN IMPORTANT LINK BETWEEN TBI AND CHRONIC NEURODEGENERATIVE DISEASES, EITHER AS A PRECIPITATING EVENT OR RELATED TO ACCUMULATION OF AD-LIKE PATHOLOGY WHICH IS AMPLIFIED IN THE CONTEXT OF AGING. THUS WITH ADVANCED AGE AND VASCULAR DYSFUNCTION, TBI CAN TRIGGER SELF-PROPAGATING CYCLES OF NEURONAL INJURY, PATHOLOGICAL PROTEIN AGGREGATION, AND SYNAPTIC LOSS RESULTING IN CHRONIC NEURODEGENERATIVE DISEASE. IN THIS REVIEW WE DISCUSS EVIDENCE SUPPORTING TBI AND AGING AS DUAL, INTERACTING RISK FACTORS FOR AD, AND THE ROLE OF ABETA AND CEREBRAL VASCULAR DYSFUNCTION IN THIS RELATIONSHIP. EVIDENCE IS DISCUSSED THAT ABETA IS INVOLVED IN CYTO- AND SYNAPTO-TOXICITY AFTER SEVERE TBI, AND THAT ITS CHRONIC EFFECTS ARE POTENTIATED BY AGING AND IMPAIRED CEREBRAL VASCULAR FUNCTION. FROM A THERAPEUTIC PERSPECTIVE, WE EMPHASIZE THAT IN THE FIELDS OF TBI- AND AGING-RELATED NEURODEGENERATION PROTECTIVE STRATEGIES SHOULD INCLUDE PRESERVATION OF NEUROVASCULAR FUNCTION. 2017 2 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 3 5580 46 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 4 6347 33 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 4130 34 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 6 6893 34 [SLEEP AND DEMENTIA]. AGING IS ASSOCIATED WITH CHANGES IN SLEEP STRUCTURE AND CEREBRAL DEPOSITION OF AMYLOID BETA AND TAU PROTEINS. SLEEP DISTURBANCES PRECEDE THE ONSET OF DEMENTIA BY YEARS. COMORBID SLEEP DISORDERS, SUCH AS INSOMNIA AND SLEEP-DISORDERED BREATHING, A FAMILY HISTORY OF DEMENTIA AND EPIGENETIC FACTORS CAN CONTRIBUTE TO THE DEVELOPMENT OF DEMENTIA. THIS ARTICLE EXPLORES THE QUESTION OF THE INTERACTION BETWEEN SLEEP AND DEMENTIA BASED ON THE EXISTING LITERATURE. ALTERATIONS CAUSED BY SLOW WAVE SLEEP LEAD TO CHANGES IN THE GLYMPHATIC CLEARANCE OF AMYLOID BETA, TAU PROTEINS AND OTHER PROTEINS. TRANSIENT AND CHRONIC SLEEP DISORDERS CAUSE DISTURBANCES IN THE BRAIN AREAS RESPONSIBLE FOR COGNITION AND BEHAVIOR. SLEEP-REGULATING BRAIN AREAS ARE THE FIRST TO BE AFFECTED IN THE NEURODEGENERATIVE PROCESS AND ACCELERATE THE RISK OF DEMENTIA. CIRCADIAN AGE-RELATED CHANGES IN AMYLOID BETA AND TAU PROTEINS AFFECT THE AMOUNT AND DEPTH OF SLEEP AND VICE VERSA. AMYLOID BETA IN CEREBROSPINAL FLUID SHOWS AN INVERSE CORRELATION WITH SLEEP. OREXINS MODULATE AMYLOID BETA AND SLEEP. 2023 7 4646 40 NEUROPATHOLOGICAL MECHANISMS ASSOCIATED WITH PESTICIDES IN ALZHEIMER'S DISEASE. ENVIRONMENTAL TOXICANTS HAVE BEEN IMPLICATED IN NEURODEGENERATIVE DISEASES, AND PESTICIDE EXPOSURE IS A SUSPECTED ENVIRONMENTAL RISK FACTOR FOR ALZHEIMER'S DISEASE (AD). SEVERAL EPIDEMIOLOGICAL ANALYSES HAVE AFFIRMED A LINK BETWEEN PESTICIDES AND INCIDENCE OF SPORADIC AD. MEANWHILE, IN VITRO AND ANIMAL MODELS OF AD HAVE SHED LIGHT ON POTENTIAL NEUROPATHOLOGICAL MECHANISMS. IN THIS PAPER, A PERSPECTIVE ON NEUROPATHOLOGICAL MECHANISMS UNDERLYING PESTICIDES' INDUCTION OF AD IS PROVIDED. PROPOSED MECHANISMS RANGE FROM GENERIC OXIDATIVE STRESS INDUCTION IN NEURONS TO MORE AD-SPECIFIC PROCESSES INVOLVING AMYLOID-BETA (ABETA) AND HYPERPHOSPHORYLATED TAU (P-TAU). MECHANISMS THAT ARE MORE SPECULATIVE OR INDIRECT IN NATURE, INCLUDING SOMATIC MUTATION, EPIGENETIC MODULATION, IMPAIRMENT OF ADULT NEUROGENESIS, AND MICROBIOTA DYSBIOSIS, ARE ALSO DISCUSSED. CHRONIC TOXICITY MECHANISMS OF ENVIRONMENTAL PESTICIDE EXPOSURE CROSSTALKS IN COMPLEX WAYS AND COULD POTENTIALLY BE MUTUALLY ENHANCING, THUS MAKING THE DECIPHERING OF SIMPLISTIC CAUSAL RELATIONSHIPS DIFFICULT. 2020 8 5837 33 STRESSED MITOCHONDRIA: A TARGET TO INTRUDE ALZHEIMER'S DISEASE. ALZHEIMER'S DISEASE (AD) IS THE INOPERABLE, INCAPACITATING, NEUROPSYCHIATRIC, AND DEGENERATIVE MANIFESTATION THAT DRASTICALLY AFFECTS HUMAN LIFE QUALITY. THE CURRENT MEDICATIONS TARGET EXTRA-NEURONAL SENILE PLAQUES, OXIDATIVE STRESS, NEUROINFLAMMATION, INTRANEURONAL NEUROFIBRILLARY TANGLES, CHOLINERGIC DEFICITS, AND EXCITOTOXICITY. AMONG NOVEL PATHWAYS AND TARGETS, BIOENERGETIC AND RESULTANT MITOCHONDRIAL DYSFUNCTION HAS BEEN RECOGNIZED AS ESSENTIAL FACTORS THAT DECIDE THE NEURONAL FATE AND CONSEQUENT NEURODEGENERATION IN AD. THE CRUCIAL ATTRIBUTES OF MITOCHONDRIA, INCLUDING BIOENERGESIS, SIGNALING, SENSING, INTEGRATING, AND TRANSMITTING BIOLOGICAL SIGNALS CONTRIBUTE TO OPTIMUM NETWORKING OF NEURONAL DYNAMICS AND MAKE THEM INDISPENSABLE FOR CELL SURVIVAL. IN AD, MITOCHONDRIAL DYSFUNCTION AND MITOPHAGY ARE A PRELIMINARY AND CRITICAL EVENT THAT AGGRAVATES THE PATHOLOGICAL CASCADE. STRESS IS KNOWN TO PROMOTE AND EXAGGERATE THE NEUROPATHOLOGICAL ALTERATION DURING NEURODEGENERATION AND METABOLIC IMPAIRMENTS, ESPECIALLY IN THE CORTICO-LIMBIC SYSTEM, BESIDES ADVERSELY AFFECTING THE NORMAL PHYSIOLOGY AND MITOCHONDRIAL DYNAMICS. STRESS INVOLVES THE ALLOCATION OF ENERGY RESOURCES FOR NEURONAL SURVIVAL. CHRONIC AND AGGRAVATED STRESS RESPONSE LEADS TO EXCESSIVE RELEASE OF GLUCOCORTICOIDS BY ACTIVATION OF THE HYPOTHALAMIC-PITUITARYADRENAL (HPA) AXIS. BY ACTING THROUGH THEIR RECEPTORS, GLUCOCORTICOIDS INFLUENCE ADVERSE MITOCHONDRIAL CHANGES AND ALTER MTDNA TRANSCRIPTION, MTRNA EXPRESSION, HIPPOCAMPAL MITOCHONDRIAL NETWORK, AND ULTIMATELY MITOCHONDRIAL PHYSIOLOGY. CHRONIC STRESS ALSO AFFECTS MITOCHONDRIAL DYNAMICS BY CHANGING METABOLIC AND NEURO-ENDOCRINAL SIGNALLING, AGGRAVATING OXIDATIVE STRESS, PROVOKING INFLAMMATORY MEDIATORS, ALTERING TROPIC FACTORS, INFLUENCING GENE EXPRESSION, AND MODIFYING EPIGENETIC PATHWAYS. THUS, EXPLORING CHRONIC STRESS-INDUCED GLUCOCORTICOID DYSREGULATION AND RESULTANT BIO-BEHAVIORAL AND PSYCHOSOMATIC MITOCHONDRIAL ALTERATIONS MAY BE A FEASIBLE NARRATIVE TO INVESTIGATE AND UNRAVEL THE MYSTERIOUS PATHOBIOLOGY OF AD. 2021 9 5541 41 ROLE OF DIETARY PHENOLS IN MITIGATING MICROGLIA-MEDIATED NEUROINFLAMMATION. CHRONIC NEUROINFLAMMATION IS A PATHOLOGICAL FEATURE OF A NUMBER OF CENTRAL NERVOUS SYSTEM (CNS) DISEASES AND IS MEDIATED BY SUSTAINED ACTIVATION OF MICROGLIAL CELLS, THE INNATE IMMUNE CELLS OF THE CNS. STUDIES HAVE MAINLY FOCUSED ON IDENTIFYING THE MOLECULAR AND EPIGENETIC MECHANISMS OF MICROGLIAL ACTIVATION. THIS IS CRUCIAL IN DESIGNING THERAPEUTIC STRATEGIES FOR NEUROPATHOLOGIES IN WHICH PROLONGED MICROGLIAL ACTIVATION IS KNOWN TO EXACERBATE DISEASE CONDITION. IN RECENT YEARS, INCREASING EVIDENCE SHOW THAT NATURALLY OCCURRING COMPOUNDS PRESENT IN REGULAR DIET COULD FUNCTION AS "NUTRACEUTICALS," ARRESTING MICROGLIAL ACTIVATION, AND THUS CONFERRING NEUROPROTECTION. THIS REVIEW SUMMARIZES OUR UNDERSTANDING OF THE ROLE OF DIETARY PHENOLIC NUTRACEUTICALS IN MITIGATING MICROGLIA-MEDIATED NEUROINFLAMMATION. STUDIES SHOW THAT THESE NATURAL PHENOLS INHIBIT KEY SIGNALING PATHWAYS IN ACTIVATED MICROGLIA SUCH AS THE NFKAPPAB, MAPK AND JAK-STAT THAT TRIGGER MICROGLIA-MEDIATED INFLAMMATION IN VARIOUS NEUROPATHOLOGICAL CONDITIONS SUCH AS INJURY, INFECTION, STROKE, AUTISM AND NEURODEGENERATIVE DISEASES, I.E., ALZHEIMER'S DISEASE AND PARKINSON'S DISEASE. THE ANTI-INFLAMMATORY AND ANTIOXIDANT EFFECT EXERTED BY THESE NATURAL PHENOLS HAVE SHOWN CONSIDERABLE SUCCESS IN IMPROVING DISEASE CONDITION IN ANIMAL MODELS OF NEUROPATHOLOGIES, AND THUS SEEM TO BE SUITABLE CANDIDATES FOR DEVELOPING THERAPEUTIC STRATEGIES. 2016 10 4682 31 NEW PATHWAYS IDENTIFY NOVEL DRUG TARGETS FOR THE PREVENTION AND TREATMENT OF ALZHEIMER'S DISEASE. ALZHEIMER'S DISEASE (AD) IS AN INCURABLE, PROGRESSIVE NEURODEGENERATIVE DISORDER. AD IS A COMPLEX AND MULTIFACTORIAL DISEASE THAT IS RESPONSIBLE FOR 60-80% OF DEMENTIA CASES. AGING, GENETIC FACTORS, AND EPIGENETIC CHANGES ARE THE MAIN RISK FACTORS FOR AD. TWO AGGREGATION-PRONE PROTEINS PLAY A DECISIVE ROLE IN AD PATHOGENESIS: BETA-AMYLOID (ABETA) AND HYPERPHOSPHORYLATED TAU (PTAU). BOTH OF THEM FORM DEPOSITS AND DIFFUSIBLE TOXIC AGGREGATES IN THE BRAIN. THESE PROTEINS ARE THE BIOMARKERS OF AD. DIFFERENT HYPOTHESES HAVE TRIED TO EXPLAIN AD PATHOGENESIS AND SERVED AS PLATFORMS FOR AD DRUG RESEARCH. EXPERIMENTS DEMONSTRATED THAT BOTH ABETA AND PTAU MIGHT START NEURODEGENERATIVE PROCESSES AND ARE NECESSARY FOR COGNITIVE DECLINE. THE TWO PATHOLOGIES ACT IN SYNERGY. INHIBITION OF THE FORMATION OF TOXIC ABETA AND PTAU AGGREGATES HAS BEEN AN OLD DRUG TARGET. RECENTLY, SUCCESSFUL ABETA CLEARANCE BY MONOCLONAL ANTIBODIES HAS RAISED NEW HOPES FOR AD TREATMENTS IF THE DISEASE IS DETECTED AT EARLY STAGES. MORE RECENTLY, NOVEL TARGETS, E.G., IMPROVEMENTS IN AMYLOID CLEARANCE FROM THE BRAIN, APPLICATION OF SMALL HEAT SHOCK PROTEINS (HSPS), MODULATION OF CHRONIC NEUROINFLAMMATION BY DIFFERENT RECEPTOR LIGANDS, MODULATION OF MICROGLIAL PHAGOCYTOSIS, AND INCREASE IN MYELINATION HAVE BEEN REVEALED IN AD RESEARCH. 2023 11 5519 41 RISK FACTORS FOR ALZHEIMER'S DISEASE: ROLE OF MULTIPLE ANTIOXIDANTS, NON-STEROIDAL ANTI-INFLAMMATORY AND CHOLINERGIC AGENTS ALONE OR IN COMBINATION IN PREVENTION AND TREATMENT. THE ETIOLOGY OF ALZHEIMER'S DISEASE (AD) IS NOT WELL UNDERSTOOD. ETIOLOGIC FACTORS, CHRONIC INFLAMMATORY REACTIONS, OXIDATIVE AND NITROSYLATIVE STRESSES AND HIGH CHOLESTEROL LEVELS ARE THOUGHT TO BE IMPORTANT FOR INITIATING AND PROMOTING NEURODEGENERATIVE CHANGES COMMONLY FOUND IN AD BRAINS. EVEN IN FAMILIAL AD, OXIDATIVE STRESS PLAYS AN IMPORTANT ROLE IN THE EARLY ONSET OF THE DISEASE. MITOCHONDRIAL DAMAGE AND PROTEASOME INHIBITION REPRESENT EARLY EVENTS IN THE PATHOGENESIS OF AD, WHEREAS INCREASED PROCESSING OF AMYLOID PRECURSOR PROTEIN (APP) TO BETA-AMYLOID (ABETA) FRAGMENTS (ABETA(40) AND ABETA(42)) AND FORMATION OF SENILE PLAQUES AND NEUROFIBRILLARY TANGLES (NFTS) REPRESENT LATE EVENTS. WE PROPOSE A HYPOTHESIS THAT IN IDIOPATHIC AD, EPIGENETIC COMPONENTS OF NEURONS SUCH AS MITOCHONDRIA, PROTEASOMES AND POST-TRANSLATION PROTEIN MODIFICATIONS (PROCESSING OF AMYLOID PRECURSOR PROTEIN TO BETA-AMYLOID AND HYPERPHOSPHORYLATION OF TAU), RATHER THAN NUCLEAR GENES, ARE THE PRIMARY TARGETS FOR THE ACTION OF DIVERSE GROUPS OF NEUROTOXINS. BASED ON EPIDEMIOLOGIC, LABORATORY AND LIMITED CLINICAL STUDIES, WE PROPOSE THAT A COMBINATION OF NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) AND APPROPRIATE LEVELS AND TYPES OF MULTIPLE MICRONUTRIENTS, INCLUDING ANTIOXIDANTS, MAY BE MORE EFFECTIVE THAN THE INDIVIDUAL AGENTS IN THE PREVENTION, AND THEY, IN COMBINATION WITH A CHOLINERGIC AGENT, MAY BE MORE EFFECTIVE IN THE TREATMENT OF AD THAN THE INDIVIDUAL AGENTS ALONE. IN ADDITION, AGENTS, WHICH CAN PREVENT FORMATION OF PLAQUES OR DISSOLVE THESE PLAQUES MAY FURTHER ENHANCE THE EFFICACY OF OUR PROPOSED TREATMENT STRATEGY. 2002 12 2874 32 FUNCTIONAL NUTRITION AS INTEGRATED INTERVENTION FOR IN- AND OUTPATIENT WITH SCHIZOPHRENIA. SCHIZOPHRENIA IS A CHRONIC AND PROGRESSIVE DISORDER CHARACTERIZED BY COGNITIVE, EMOTIONAL,AND BEHAVIORAL ABNORMALITIES ASSOCIATED WITH NEURONAL DEVELOPMENT AND SYNAPTIC PLASTICITY ALTERATIONS. GENETIC AND EPIGENETIC ABNORMALITIES IN CORTICAL PARVALBUMIN-POSITIVE GABAERGIC INTERNEURONS AND CONSEQUENT ALTERATIONS IN GLUTAMATE-MEDIATED EXCITATORY NEUROTRANSMISSION DURING EARLY NEURODEVELOPMENT UNDERLIE SCHIZOPHRENIA MANIFESTATION AND PROGRESSION. ALSO, EPIGENETIC ALTERATIONS DURING PREGNANCY OR EARLY PHASES OF POSTNATAL LIFE ARE ASSOCIATED WITH SCHIZOPHRENIA VULNERABILITY AND IN-FLAMMATORY PROCESSES, WHICH ARE AT THE BASIS OF BRAIN PATHOLOGY AND A HIGHER RISK OF COMORBIDITIES, INCLUDING CARDIOVASCULAR DISEASES AND METABOLIC SYNDROME. IN ADDITION, SCHIZOPHRENIA PATIENTS ADOPT AN UNHEALTHY LIFESTYLE AND POOR NUTRITION, LEADING TO PREMATURE DEATH. HERE, I EXPLORED THE ROLE OF FUNCTIONAL NUTRITION AS AN INTEGRATED INTERVENTION FOR THE LONG-TERM MANAGEMENT OF PATIENTS WITH SCHIZOPHRENIA. SEVERAL NATURAL BIOACTIVE COMPOUNDS IN PLANT-BASED WHOLE FOODS, INCLUDING FLAVONOIDS, PHYTONUTRIENTS, VITAMINS, FATTY ACIDS, AND MINERALS, MODULATE BRAIN FUNCTIONING BY TARGETING NEUROINFLAMMATION AND IMPROVING COGNITIVE DECLINE. ALTHOUGH FURTHER CLINICAL STUDIES ARE NEEDED, A FUNCTIONAL DIET RICH IN NATURAL BIOACTIVE COMPOUNDS MIGHT BE EFFECTIVE IN SYNERGISM WITH STANDARD TREATMENTS TO IMPROVE SCHIZOPHRENIA SYMPTOMS AND REDUCE THE RISK OF COMORBIDITIES. 2023 13 2350 38 EPIGENETIC REGULATION OF NEUROINFLAMMATION IN PARKINSON'S DISEASE. NEUROINFLAMMATION IS ONE OF THE MOST SIGNIFICANT FACTORS INVOLVED IN THE INITIATION AND PROGRESSION OF PARKINSON'S DISEASE. PD IS A NEURODEGENERATIVE DISORDER WITH A MOTOR DISABILITY LINKED WITH VARIOUS COMPLEX AND DIVERSIFIED RISK FACTORS. THESE FACTORS TRIGGER MYRIADS OF CELLULAR AND MOLECULAR PROCESSES, SUCH AS MISFOLDING DEFECTIVE PROTEINS, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, AND NEUROTOXIC SUBSTANCES THAT INDUCE SELECTIVE NEURODEGENERATION OF DOPAMINE NEURONS. THIS NEURONAL DAMAGE ACTIVATES THE NEURONAL IMMUNE SYSTEM, INCLUDING GLIAL CELLS AND INFLAMMATORY CYTOKINES, TO TRIGGER NEUROINFLAMMATION. THE TRANSITION OF ACUTE TO CHRONIC NEUROINFLAMMATION ENHANCES THE SUSCEPTIBILITY OF INFLAMMATION-INDUCED DOPAMINERGIC NEURON DAMAGE, FORMING A VICIOUS CYCLE AND PROMPTING AN INDIVIDUAL TO PD DEVELOPMENT. EPIGENETIC MECHANISMS RECENTLY HAVE BEEN AT THE FOREFRONT OF THE REGULATION OF NEUROINFLAMMATORY FACTORS IN PD, PROPOSING A NEW DAWN FOR BREAKING THIS VICIOUS CYCLE. THIS REVIEW EXAMINED THE CORE EPIGENETIC MECHANISMS INVOLVED IN THE ACTIVATION AND PHENOTYPIC TRANSFORMATION OF GLIAL CELLS MEDIATED NEUROINFLAMMATION IN PD. WE FOUND THAT EPIGENETIC MECHANISMS DO NOT WORK INDEPENDENTLY, DESPITE BEING COORDINATED WITH EACH OTHER TO ACTIVATE NEUROINFLAMMATORY PATHWAYS. IN THIS REGARD, WE ATTEMPTED TO FIND THE SYNERGIC CORRELATION AND CONTRIBUTION OF THESE EPIGENETIC MODIFICATIONS WITH VARIOUS NEUROINFLAMMATORY PATHWAYS TO BROADEN THE CANVAS OF UNDERLYING PATHOLOGICAL MECHANISMS INVOLVED IN PD DEVELOPMENT. MOREOVER, THIS STUDY HIGHLIGHTED THE DUAL CHARACTERISTICS (NEUROPROTECTIVE/NEUROTOXIC) OF THESE EPIGENETIC MARKS, WHICH MAY COUNTERACT PD PATHOGENESIS AND MAKE THEM POTENTIAL CANDIDATES FOR DEVISING FUTURE PD DIAGNOSIS AND TREATMENT. 2021 14 676 46 BRAIN AGING: A IANUS-FACED PLAYER BETWEEN HEALTH AND NEURODEGENERATION. NEURODEGENERATIVE DISEASES ARE INCURABLE DEBILITATING DISORDERS CHARACTERIZED BY STRUCTURAL AND FUNCTIONAL NEURONAL LOSS. APPROXIMATELY 30 MILLION PEOPLE ARE AFFECTED WORLDWIDE, AND THIS NUMBER IS PREDICTED TO REACH MORE THAN 150 MILLION BY 2050. NEURODEGENERATIVE DISORDERS INCLUDE ALZHEIMER'S, PARKINSON'S, AND PRION DISEASES AMONG OTHERS. THESE DISORDERS ARE CHARACTERIZED BY THE ACCUMULATION OF AGGREGATING PROTEINS FORMING AMYLOID, RESPONSIBLE FOR THE DISEASE-ASSOCIATED PATHOLOGICAL LESIONS. THE AGGREGATION OF AMYLOIDOGENIC PROTEINS CAN RESULT EITHER IN GAINING OF TOXIC FUNCTIONS, DERIVED FROM THE DAMAGE PROVOKED BY THESE DEPOSITS IN AFFECTED TISSUE, OR IN A LOSS OF FUNCTIONS, DUE TO THE SEQUESTRATION AND THE CONSEQUENT INABILITY OF THE AGGREGATING PROTEIN TO ENSURE ITS PHYSIOLOGICAL ROLE. WHILE IT IS WIDELY ACCEPTED THAT AGING REPRESENTS THE MAIN RISK FACTOR FOR NEURODEGENERATION, THERE IS STILL NO CLEAR CUT-OFF LINE BETWEEN THE TWO CONDITIONS. INDEED, MANY OF THE PATHWAYS THAT ARE COMMONLY ALTERED IN NEURODEGENERATION-MISFOLDED PROTEIN ACCUMULATION, CHRONIC INFLAMMATION, MITOCHONDRIAL DYSFUNCTION, IMPAIRED IRON HOMEOSTASIS, EPIGENETIC MODIFICATIONS-HAVE BEEN OFTEN CORRELATED ALSO WITH HEALTHY AGING. THIS OVERLAP COULD BE EXPLAINED BY THE FACT THAT THE CONTINUOUS ACCUMULATION OF CELLULAR DAMAGES, TOGETHER WITH A PROGRESSIVE DECLINE IN METABOLIC EFFICIENCY DURING AGING, MAKES THE NEURONS MORE VULNERABLE TO TOXIC INJURIES. WHEN A GIVEN THRESHOLD IS EXCEEDED, ALL THESE ALTERATIONS MIGHT GIVE RISE TO PATHOLOGICAL PHENOTYPES THAT ULTIMATELY LEAD TO NEURODEGENERATION. 2020 15 6897 20 [TELOMERE-TELOMERASE SYSTEM IN AGING, NORM AND PATHOLOGY (LITERATURE REVIEW)]. THIS LITERATURE REVIEW PRESENTS RESULTS OF RESEARCH SHOWING ASSOCIATION BETWEEN FUNCTIONAL ACTIVITY OF THE TELOMERE-TELOMERASE SYSTEM AND MENTAL COGNITIVE AND EMOTIONAL PROCESSES IN NORMAL AND VARIOUS PATHOLOGICAL STATES: CHRONIC STRESS, DEPRESSION, BIPOLAR DISORDER, SCHIZOPHRENIA, MILD COGNITIVE IMPAIRMENT AND DEMENTIA IN AGING. IT ALSO REFERS TO AGE-SPECIFIC, PSYCHO-SOCIAL, ECONOMIC, IMMUNOLOGICAL, GENETIC AND EPIGENETIC FACTORS THAT INFLUENCE THESE RELATIONSHIPS. 2017 16 6728 32 VOLTAGE-GATED CALCIUM CHANNELS AND PARKINSON'S DISEASE. A COMPLEX INTERACTION OF ENVIRONMENTAL, GENETIC AND EPIGENETIC FACTORS COMBINE WITH AGEING TO CAUSE THE MOST PREVALENT OF MOVEMENT DISORDERS PARKINSON'S DISEASE. CURRENT PHARMACOLOGICAL TREATMENTS ONLY TACKLE THE SYMPTOMS AND DO NOT STOP PROGRESSION OF THE DISEASE OR REVERSE THE NEURODEGENERATIVE PROCESS. WHILE SOME INCIDENCES OF PARKINSON'S DISEASE ARISE THROUGH HERITABLE GENETIC DEFECTS, THE CAUSE OF THE MAJORITY OF CASES REMAINS UNKNOWN. LIKEWISE, WHY SOME NEURONAL POPULATIONS ARE MORE SUSCEPTIBLE TO NEURODEGENERATION THAN OTHERS IS NOT CLEAR, BUT AS THE MOLECULAR PATHWAYS RESPONSIBLE FOR THE PROCESS OF CELL DEATH ARE UNRAVELLED, IT IS INCREASINGLY APPARENT THAT DISRUPTED CELLULAR ENERGY METABOLISM PLAYS A CENTRAL ROLE. PRECISE CONTROL OF CELLULAR CALCIUM CONCENTRATIONS IS CRUCIAL FOR MAINTENANCE OF ENERGY HOMEOSTASIS. RECENTLY, DIFFERENTIAL CELLULAR EXPRESSION OF NEURONAL VOLTAGE-GATED CALCIUM CHANNEL (CA(V)) ISOFORMS HAS BEEN IMPLICATED IN THE SUSCEPTIBILITY OF VULNERABLE NEURONS TO NEURODEGENERATION IN PARKINSON'S DISEASE. CA(V) CHANNELS ARE ALSO INVOLVED IN THE SYNAPTIC PLASTICITY RESPONSE TO THE DENERVATION THAT OCCURS IN PARKINSON'S DISEASE AND FOLLOWING CHRONIC TREATMENT WITH ANTI-PARKINSONIAN DRUGS. THIS REVIEW WILL EXAMINE THE PUTATIVE ROLE NEURONAL CA(V) CHANNELS HAVE IN THE PATHOGENESIS AND TREATMENT OF PARKINSON'S DISEASE. 2012 17 5280 36 PROMOTING SYMPATHOVAGAL BALANCE IN MULTIPLE SCLEROSIS; PHARMACOLOGICAL, NON-PHARMACOLOGICAL, AND SURGICAL STRATEGIES. ACCUMULATED EVIDENCE SUGGESTS THAT CARDIOVASCULAR AUTONOMIC NERVOUS SYSTEM (ANS) DYSFUNCTION MAY BE THE UNDERLYING CAUSE OF MANY MS CLINICAL PRESENTATIONS, INCLUDING NEURODEGENERATION AND REDUCED RESPONSE TO IMMUNOMODULATORY THERAPIES, DEPRESSION, FATIGUE AND SLEEP DISORDERS, MIGRAINE, OSTEOPOROSIS, AND CHRONIC CEREBROSPINAL VENOUS INSUFFICIENCY, THE NEWER MS VASCULAR ETIOLOGY. WE HAVE RECENTLY DESCRIBED THE GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS WITH THE POTENTIAL INFLUENCING ANS ACTIVITY, AND THE INTERACTIONS AMONG THESE FACTORS. THIS REVIEW EXPANDS UPON PREVIOUS ONES, DESCRIBING THE PHARMACOLOGICAL, NON-PHARMACOLOGICAL, AND SURGICAL STRATEGIES THAT COULD BE ADOPTED TO PREVENT AND MINIMIZE THE DETERIORATION IN ANS FUNCTION, PROMOTING A STATE OF SYMPATHOVAGAL BALANCE. HOWEVER, THESE STRATEGIES SHOULD NOT BE APPLIED AS "ONE SIZE FITS ALL", BUT SHOULD TAKE INTO ACCOUNT THE NATURE AND THE DEGREE OF ANS DYSFUNCTION. THESE STRATEGIES WOULD BE EFFECTIVE IN IMPROVING ANS FUNCTION NOT ONLY IN MS, BUT ALSO IN OTHER AUTOIMMUNE AND NEURODEGENERATIVE DISEASES, WHERE THE DYSFUNCTION OF THIS SYSTEM PLAYS A ROLE. 2016 18 5351 33 RATIONALE FOR DIETARY ANTIOXIDANT TREATMENT OF ADHD. INCREASING UNDERSTANDING ARISES REGARDING DISADVANTAGES OF STIMULANT MEDICATION IN CHILDREN WITH ADHD (ATTENTION-DEFICIT HYPERACTIVITY DISORDER). THIS REVIEW PRESENTS SCIENTIFIC FINDINGS SUPPORTING DIETARY ANTIOXIDANT TREATMENT OF ADHD AND DESCRIBES SUBSTANTIAL ALTERATIONS IN THE IMMUNE SYSTEM, EPIGENETIC REGULATION OF GENE EXPRESSION, AND OXIDATIVE STRESS REGULATION IN ADHD. AS A RESULT, CHRONIC INFLAMMATION AND OXIDATIVE STRESS COULD DEVELOP, WHICH CAN LEAD TO ADHD SYMPTOMS, FOR EXAMPLE BY CHRONIC T-CELL-MEDIATED NEUROINFLAMMATION, AS WELL AS BY NEURONAL OXIDATIVE DAMAGE AND LOSS OF NORMAL CEREBRAL FUNCTIONS. THEREFORE, MODULATION OF IMMUNE SYSTEM ACTIVITY AND OXIDANT-ANTIOXIDANT BALANCE USING NUTRITIONAL APPROACHES MIGHT HAVE POTENTIAL IN ADHD TREATMENT. THE USE OF NATURAL ANTIOXIDANTS AGAINST OXIDATIVE CONDITIONS IS AN EMERGING FIELD IN THE MANAGEMENT OF NEURODEGENERATIVE DISEASES. DIETARY POLYPHENOLS, FOR EXAMPLE, HAVE ANTIOXIDANT CAPACITIES AS WELL AS IMMUNOREGULATORY EFFECTS AND, THEREFORE, APPEAR APPROPRIATE IN ADHD THERAPY. THIS REVIEW CAN STIMULATE THE DEVELOPMENT AND INVESTIGATION OF DIETARY ANTIOXIDANT TREATMENT IN ADHD, WHICH IS HIGHLY DESIRED. 2018 19 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 20 5033 37 PESTICIDES AND HUMAN CHRONIC DISEASES: EVIDENCES, MECHANISMS, AND PERSPECTIVES. ALONG WITH THE WIDE USE OF PESTICIDES IN THE WORLD, THE CONCERNS OVER THEIR HEALTH IMPACTS ARE RAPIDLY GROWING. THERE IS A HUGE BODY OF EVIDENCE ON THE RELATION BETWEEN EXPOSURE TO PESTICIDES AND ELEVATED RATE OF CHRONIC DISEASES SUCH AS DIFFERENT TYPES OF CANCERS, DIABETES, NEURODEGENERATIVE DISORDERS LIKE PARKINSON, ALZHEIMER, AND AMYOTROPHIC LATERAL SCLEROSIS (ALS), BIRTH DEFECTS, AND REPRODUCTIVE DISORDERS. THERE IS ALSO CIRCUMSTANTIAL EVIDENCE ON THE ASSOCIATION OF EXPOSURE TO PESTICIDES WITH SOME OTHER CHRONIC DISEASES LIKE RESPIRATORY PROBLEMS, PARTICULARLY ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), CARDIOVASCULAR DISEASE SUCH AS ATHEROSCLEROSIS AND CORONARY ARTERY DISEASE, CHRONIC NEPHROPATHIES, AUTOIMMUNE DISEASES LIKE SYSTEMIC LUPUS ERYTHEMATOUS AND RHEUMATOID ARTHRITIS, CHRONIC FATIGUE SYNDROME, AND AGING. THE COMMON FEATURE OF CHRONIC DISORDERS IS A DISTURBANCE IN CELLULAR HOMEOSTASIS, WHICH CAN BE INDUCED VIA PESTICIDES' PRIMARY ACTION LIKE PERTURBATION OF ION CHANNELS, ENZYMES, RECEPTORS, ETC., OR CAN AS WELL BE MEDIATED VIA PATHWAYS OTHER THAN THE MAIN MECHANISM. IN THIS REVIEW, WE PRESENT THE HIGHLIGHTED EVIDENCE ON THE ASSOCIATION OF PESTICIDE'S EXPOSURE WITH THE INCIDENCE OF CHRONIC DISEASES AND INTRODUCE GENETIC DAMAGES, EPIGENETIC MODIFICATIONS, ENDOCRINE DISRUPTION, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, ENDOPLASMIC RETICULUM STRESS AND UNFOLDED PROTEIN RESPONSE (UPR), IMPAIRMENT OF UBIQUITIN PROTEASOME SYSTEM, AND DEFECTIVE AUTOPHAGY AS THE EFFECTIVE MECHANISMS OF ACTION. 2013