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Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders
Open accessAbstract
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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“First, axonal degeneration, which is a precursor to many age-related neuronal disorders140,141, is characterized by rapid NAD+ depletion.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [140]
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Metadata
- Authors
- Salvadores, N., Sanhueza, M., Manque, P., & Court, F. A.
- Affiliations
- Universidad Mayor (CL)
- Corresponding author
- 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)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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