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Cited by 362Autophagy in Disease and TherapyLysosomal Storage Disorders ResearchCellular transport and secretion

Neurodegenerative lysosomal disorders: A continuum from development to late age

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Nixon, Ralph A., Yang, Dun-Sheng, Lee, Ju-Hyun·2008·Autophagy
DOI 10.4161/auto.6259
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Abstract

Neuronal survival requires continuous lysosomal turnover of cellular constituents delivered by autophagy and endocytosis. Primary lysosomal dysfunction in inherited congenital "lysosomal storage" disorders is well known to cause severe neurodegenerative phenotypes associated with accumulations of lysosomes and autophagic vacuoles (AVs). Recently, the number of inherited adult-onset neurodegenerative diseases caused by proteins that regulate protein sorting and degradation within the endocytic and autophagic pathways has grown considerably. In this Perspective, we classify a group of neurodegenerative diseases across the lifespan as disorders of lysosomal function, which feature extensive autophagic-endocytic-lysosomal neuropathology and may share mechanisms of neurodegeneration related to degradative failure and lysosomal destabilization. We highlight Alzheimer's disease as a disease within this group and discuss how each of the genes and other risk factors promoting this disease contribute to progressive lysosomal dysfunction and neuronal cell death.

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  • Insufficient degradation of protein aggregates and chronic inflammation are driving forces of AD and PD brain pathology.

    “Growing evidence indicates that insufficient degradation of protein aggregates and chronic inflammation are driving forces of AD and PD brain pathology [30–32].”

    From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [30]

    The sections on pathological consequences in Alzheimer’s disease and lysosomal-system defects in Parkinson disease link impaired protein degradation to AD pathology and impaired α-synuclein degradation to familial PD. They do not support the additional claim that chronic inflammation drives pathology in either disease. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Nixon, R. A., Yang, D.-S., & Lee, J.-H.
Affiliations
  • New York University (US)
  • Nathan Kline Institute for Psychiatric Research (US)
ORCID
Venue
Autophagy
Publisher
Informa UK Limited
Published
2008-06-02
Volume
4
Issue
5
Pages
590-599
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
DOI
10.4161/auto.6259
OpenAlex
W2119141725
Cited by
362
References
22
Citations by year
2026: 3 · 2025: 8 · 2024: 12 · 2023: 12 · 2022: 23 · 2021: 18 · 2020: 26 · 2019: 28 · 2018: 22 · 2017: 20 · 2016: 20 · 2015: 22 · 2014: 20 · 2013: 24 · 2012: 32
FWCI
2.57
Type
journal article
Language
en
Open access
Locations
  • Autophagy (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Alzheimer's Association
  • National Institute on Aging (P01AG017617)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
lysosomal storage disease, endocytosis, autophagosomes, lysosomal dysfunction, Alzheimer's disease, protein degradation, neuronal cell death, lysosomal destabilization
MeSH terms
Aging, Alzheimer Disease, Animals, Autophagy, Humans, Lysosomes, Lysosomal Storage Diseases, Neurodegenerative Diseases

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