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Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease
Open accessAbstract
• Introduction • Innate immune response in the AD brain - Microglia - Astrocyte • Glial cells mediate the peripheral immune response in AD - Glial cell interaction with endothelial cells - Glial cell interaction with T cells • Glial cell activation as a therapeutic target in AD • Conclusion Alzheimer's disease (AD) affects more than 18 million people worldwide and is characterized by progressive memory deficits, cognitive impairment and personality changes. The main cause of AD is generally attributed to the increased production and accumulation of amyloid-β (Aβ), in association with neurofibrillary tangle (NFT) formation. Increased levels of pro-inflammatory factors such as cytokines and chemokines, and the activation of the complement cascade occurs in the brains of AD patients and contributes to the local inflammatory response triggered by senile plaque. The existence of an inflammatory component in AD is now well known on the basis of epidemiological findings showing a reduced prevalence of the disease upon long-term medication with anti-inflammatory drugs, and evidence from studies of clinical materials that shows an accumulation of activated glial cells, particularly microglia and astrocytes, in the same areas as amyloid plaques. Glial cells maintain brain plasticity and protect the brain for functional recovery from injuries. Dysfunction of glial cells may promote neurodegeneration and, eventually, the retraction of neuronal synapses, which leads to cognitive deficits. The focus of this review is on glial cells and their diversity properties in AD.
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“T-helper 1 cells can promote microglial cell activation through the secretion of IFN-γ, which also up-regulates the expression major histocompatibility complex class II molecules by microglial cells, thereby enhancing the interaction between T cells and microglial cells [164, 165].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [164]
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“T-helper 1 cells can promote microglial cell activation through the secretion of IFN-γ, which also up-regulates the expression major histocompatibility complex class II molecules by microglial cells, thereby enhancing the interaction between T cells and microglial cells [164, 165].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [164]
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“It is also known that glial cells can mediate the permeability of blood brain barrier to recruit specialized immune cells from the periphery such as T cells [164].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [164]
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“[41] Farfara D, Lifshitz V, Frenkel D.”
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“While glial cells play an essential role in maintaining normal brain function during physiologic conditions (Farfara et al., 2008 ), they are capable of inducing the secretion of several inflammatory mediators that provoke pathological changes in the CNS when activated (Benarroch, 2013 ; Forman et…”
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Multiple cytokines are involved in the early events leading to the Alzheimer's disease pathology.
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“Several studies have shown that brain cells like microglia and astrocytes induce and release diverse inflammatory mediators in response to proinflammatory factors([5-7]).”
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“In contrast to the periventricular areas, GFAP-IR and S100B-IR colocalization in astrocytes was lower in cortical areas maybe because of its state of activation since GFAP is a marker for activated astrocytes [41,42].”
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“also promote delayed neuronal damage by generating cytotoxic agents, such as proinflammatory cytokines(33,34); thus microglial cells have neuroprotective and neurotoxic properties.(35) In our system, it appears that microglial cells hold neurotoxic properties, as neuronal damage that recruits microglia is an early eve…”
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“Farfara et al (30) found high levels of CCL2 in the cerebrospinal fluid of people with Alzheimer's.”
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Muresanu, D. F. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01020.x · Cited by 2
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“Studies have shown [6] that cyclic AMP response element binding protein (CREB) is a transcription factor in long-term memory, and phosphorylation is its activated form (p-CREB).”
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Neuroprotective activity of guanosine in an in vitro model of Alzheimer's disease
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Metadata
- Authors
- Farfara, D., Lifshitz, V., & Frenkel, D.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Frenkel, D.
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2008-05-21
- Volume
- 12
- Issue
- 3
- Pages
- 762-780
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC4401126
- OpenAlex
- W2022388884
- Cited by
- 216
- References
- 202
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 10 · 2020: 13 · 2019: 5 · 2018: 7 · 2017: 9 · 2016: 7 · 2015: 8 · 2014: 15 · 2013: 15 · 2012: 20
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, glial cells, microglia, astrocytes, neuroinflammation, innate immune response, amyloid-beta, neurofibrillary tangles, amyloid plaques, complement system, cytokines and chemokines, neuroprotection, neurotoxicity, neurodegeneration, anti-inflammatory therapy
- MeSH terms
- Alzheimer Disease, Amyloid, Animals, Astrocytes, Brain, Disease Models, Animal, Humans, Models, Neurological, Synaptic Transmission, Synapses, T-Lymphocytes, Amyloid beta-Peptides, Microglia, Endothelial Cells, Plaque, Amyloid
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