An Insight into Cellular and Molecular Mechanisms Underlying the Pathogenesis of Neurodegeneration in Alzheimer’s Disease

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1398 - 1398

Published: May 8, 2023

Alzheimer’s disease (AD) is the most prominent neurodegenerative disorder in aging population. It characterized by cognitive decline, gradual neurodegeneration, and development of amyloid-β (Aβ)-plaques neurofibrillary tangles, which constitute hyperphosphorylated tau. The early stages neurodegeneration AD include loss neurons, followed synaptic impairment. Since discovery AD, substantial factual research has surfaced that outlines disease’s causes, molecular mechanisms, prospective therapeutics, but a successful cure for not yet been discovered. This may be attributed to complicated pathogenesis absence well-defined mechanism, constrained diagnostic resources treatment options. To address aforementioned challenges, extensive modeling essential fully comprehend underlying mechanisms making it easier design develop effective strategies. Emerging evidence over past few decades supports critical role Aβ tau participation glial cells different cellular pathways. review extensively discusses current understanding concerning Aβ- tau-associated dysfunction AD. Moreover, risk factors associated with including genetics, aging, environmental variables, lifestyle habits, medical conditions, viral/bacterial infections, psychiatric have summarized. present study will entice researchers more thoroughly explore status mechanism assist drug forthcoming era.

Language: Английский

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Axonal energy metabolism, and the effects in aging and neurodegenerative diseases

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: July 20, 2023

Abstract Human studies consistently identify bioenergetic maladaptations in brains upon aging and neurodegenerative disorders of (NDAs), such as Alzheimer’s disease, Parkinson’s Huntington’s Amyotrophic lateral sclerosis. Glucose is the major brain fuel glucose hypometabolism has been observed regions vulnerable to NDAs. Many susceptible are topological central hub connectome, linked by densely interconnected long-range axons. Axons, key components have high metabolic needs support neurotransmission other essential activities. Long-range axons particularly injury, neurotoxin exposure, protein stress, lysosomal dysfunction, etc. Axonopathy often an early sign neurodegeneration. Recent ascribe axonal maintenance failures local dysregulation. With this review, we aim stimulate research exploring metabolically oriented neuroprotection strategies enhance or normalize bioenergetics NDA models. Here start summarizing evidence from human patients animal models reveal correlation between connectomic disintegration aging/NDAs. To encourage mechanistic investigations on how dysregulation occurs during aging/NDAs, first review current literature distinct subdomains: axon initial segments, myelinated arbors harboring pre-synaptic boutons. In each subdomain, focus organization, activity-dependent regulation system, external glial support. Second, mechanisms regulating nicotinamide adenine dinucleotide (NAD + ) homeostasis, molecule for energy metabolism processes, including NAD biosynthetic, recycling, consuming pathways. Third, highlight innate vulnerability connectome discuss its perturbation As deficits developing into NDAs, especially asymptomatic phase, they likely exaggerated further impaired energetic cost neural network hyperactivity, pathology. Future interrogating causal relationship vulnerability, axonopathy, amyloid/tau pathology, cognitive decline will provide fundamental knowledge therapeutic interventions.

Language: Английский

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Review on anti-alzheimer drug development: approaches, challenges and perspectives

RSC Advances, Journal Year: 2024, Volume and Issue: 14(16), P. 11057 - 11088

Published: Jan. 1, 2024

Alzheimer has many crucial factors that should be considered in order to get better results from clinical trials. Benzimidazole and its isosteres represent significant scaffolds for designing potential multi-target anti-alzheimer molecules.

Language: Английский

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Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders

Frontiers in Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: Sept. 3, 2017

Aging constitutes the main risk factor for development of neurodegenerative diseases. This represents a major health issue worldwide that is only expected to escalate due ever-increasing life expectancy population. Interestingly, axonal degeneration, which occurs at early stages disorders (ND) such as Alzheimer’s disease, Amyotrophic lateral sclerosis and Parkinson’s also takes place consequence normal aging. Moreover, alteration several cellular processes proteostasis, response stress mitochondrial homeostasis, have been described occur in aging brain, can contribute pathology. Compelling evidence indicate degeneration axons precedes clinical symptoms NDs before cell body loss, constituting an event pathological process providing potential therapeutic target treat neurodegeneration neuronal death. Although are two closely linked, molecular basis switch triggers transition from healthy remains unrevealed. In this review we discuss role provide detailed overview literature current advances understanding changes during promote then context ND.

Language: Английский

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A Greek Tragedy: The Growing Complexity of Alzheimer Amyloid Precursor Protein Proteolysis

Journal of Biological Chemistry, Journal Year: 2016, Volume and Issue: 291(37), P. 19235 - 19244

Published: July 30, 2016

Language: Английский

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