Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders
Open accessAbstract
The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a “hostile” environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.
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Glial cells are critical support cells for neurons, and their loss can induce neuronal dysfunction.
“It is well known that glial cells are critical support cells for neurons [159], and that their loss can induce neuronal dysfunction [72].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [72]
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Heritability: Genes × Environment
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- Authors
- Kaminsky, N., Bihari, O., Kanner, S., & Barzilai, A.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Kanner, Sivan
- Barzilai, Ari
- Venue
- Genomics, Proteomics & Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-05-28
- Volume
- 14
- Issue
- 3
- Pages
- 155-165
- ISSN
- 1672-0229 (ISSN-L)
- 2210-3244
- PMC
- PMC4936608
- OpenAlex
- W2412822495
- Cited by
- 38
- References
- 120
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 8 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 1
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Genomics Proteomics & Bioinformatics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Israel Science Foundation (549/12, 421/15)
- German Israeli Foundation (I-192-418.13-2014)
- Joint Italian-Israeli Laboratory on Application of Neuroscience (590308)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- DNA damage response, glial dysfunction, neurodegeneration, astrocytes, microglia, oligodendrocytes, Parkinson's disease, Alzheimer's disease, Huntington's disease, genomic instability, premature aging, neuronal cell death
- MeSH terms
- Animals, Astrocytes, DNA Repair, Humans, Neuroglia, Cell Cycle Proteins, Neurodegenerative Diseases, Genomic Instability, Ataxia Telangiectasia Mutated Proteins
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