Glia in neurodegeneration: Drivers of disease or along for the ride?
Open accessAbstract
While much of the research on neurodegenerative diseases has focused on neurons, non-neuronal cells are also affected. The extent to which glia and other non-neuronal cells are causally involved in disease pathogenesis versus more passively responding to disease is an area of active research. This is complicated by the fact that there is rarely one known cause of neurodegenerative diseases; rather, these disorders likely involve feedback loops that perpetuate dysfunction. Here, we will review genetic as well as experimental evidence that suggest that non-neuronal cells are at least partially driving disease pathogenesis in numerous neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and Parkinson's disease.
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Non-cell autonomous mechanisms can cause dysfunction across the entire substantia nigra pars compacta, leading to rapid dopaminergic neurodegeneration, in contrast to neuron-specific cell autonomous mechanisms.
“in contrast to neuron-specific cell autonomous mechanisms that affect individual DA neurons within the SNc, non-cell autonomous mechanisms can cause dysfunction across the entire SNc, thereby leading to rapid DA neurodegeneration”
From Mitochondrial DNA Damage in Substantia Nigra Pars Compacta Astrocytes Exacerbates Dopaminergic Neuron Loss in a 6-Hydroxydopamine Mouse Model of Parkinsonism (2026) · cites this paper as Gleichman and Carmichael 2020
Section 3.5 (Parkinson’s disease; page not provided) discusses glial involvement in neurodegeneration and suggests that microglial reactivity may drive PD pathogenesis. It does not say that non-cell-autonomous mechanisms cause dysfunction across the entire substantia nigra pars compacta or rapid dopaminergic neurodegeneration, nor does it make the stated comparison with neuron-specific mechanisms. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn neurodegenerative diseases, microglial activation may accentuate neuron loss by promoting and propagating regional and local neuroinflammation.
“In neurodegenerative diseases, microglial activation may accentuate neuron loss by promoting and propagating regional and local neuroinflammation [420,421].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [420]
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Autophagy and ALS: mechanistic insights and therapeutic implications
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“tion may accentuate neuron loss by promoting and propagating regional and local neuroinflammation [420,421].”
BackgroundNeuron-Astrocyte Interactions in Parkinson’s Disease
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- Authors
- Gleichman, A. J., & Carmichael, S. T.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Gleichman, Amy J.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 142
- Pages
- 104957
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W3033978592
- Cited by
- 90
- References
- 127
- Citations by year
- 2026: 5 · 2025: 19 · 2024: 13 · 2023: 19 · 2022: 14 · 2021: 12 · 2020: 8
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- American Federation for Aging Research
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- glia, neurodegeneration, pathogenesis, non-neuronal cells, glial dysfunction, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, Parkinson's disease, feedback loops
- MeSH terms
- Animals, Astrocytes, Brain, Humans, Neuroglia, Neurons, Neurodegenerative Diseases
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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.
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