Cited by 182Alzheimer's disease research and treatmentsGenetics, Aging, and Longevity in Model OrganismsMitochondrial Function and Pathology

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Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders

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Salvadores, Natalia, Sanhueza, Mario, Manque, Patricio, Court, Felipe A.·2017·Frontiers in Neuroscience

DOI 10.3389/fnins.2017.00451PMC PMC5591337

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Abstract

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

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Figure 1 The seven pillars of aging in the context of neuronal and axonal degeneration. Each pillar associated to the aging process is represented in a colored box. Most relevant pathways and molecules misregulated during aging are highlighted in each box, altogether with the consequences in neuronal senescence and axonal degeneration. A misregulated response to macromolecular damage and inflammation lead to increased ROS and a decrease in available NAD+, triggering axonal degeneration. Aging also decreases the number of neuronal stem cells (NSCs) and their regenerative capability. Caloric restriction works in a protective way against aging with a mechanism opposite to the one observed with the age-linked disruption of circadian rhythm. Altered DNA modification and repair trigger pro-senescence phenotypes that lead to neuronal death, same phenotype induced by decrease of response to stress stimuli and oxidative damage.CC BY · PubMed Central

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Authors: Salvadores, N., Sanhueza, M., Manque, P., & Court, F. A.
Affiliations: Universidad Mayor (CL)
Corresponding author: Court, Felipe A.
ORCID: Salvadores, Natalia
Sanhueza, Mario
Court, Felipe A.
Venue: Frontiers in Neuroscience
Publisher: Frontiers Media SA
Published: 2017-09-04
Volume: 11
Pages: 451-451
ISSN: 1662-453X (ISSN-L)
DOI: 10.3389/fnins.2017.00451
PMC: PMC5591337
OpenAlex: W2740768704
Semantic Scholar: 6954583ab5a9e498ecf5cde38c09b1e4621405f8
Cited by: 182
References: 330
Citations by year: 2026: 17 · 2025: 18 · 2024: 21 · 2023: 18 · 2022: 30 · 2021: 24 · 2020: 25 · 2019: 15 · 2018: 14
FWCI: 1.81
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Neuroscience (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Americanae (AECID Library) (submittedVersion, cc-by-nc-nd)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
Funders: International Development Research Centre
Israel Science Foundation
Azrieli Foundation
Canadian Institutes of Health Research
Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (15150012, /FONDAP/15150012)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords: axonal degeneration, aging, neurodegenerative diseases, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, proteostasis, cellular stress response, mitochondrial homeostasis, therapeutic target

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Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders

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