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Astrocytes in Neurodegeneration

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Astrocytes-in-Neurodegeneration

Pathway Description:

Astrocytes, a subset of glial cells named for their star-shaped appearance, are the most abundant cell type in the central nervous system (CNS). Astrocytes play a highly neuroprotective role in the brain by providing neuronal maintenance and support, notably at the blood-brain barrier. Astrocytes also participate in synaptic transmission and neuroinflammatory responses, and serve as the brain’s main source of the apolipoprotein ApoE and cholesterol, which, exported via the ABCA1 transporter, is critical to membrane integrity. Normally, astrocytes aid in Aβ clearance through ApoE production, which positively facilitates Aβ clearance by excretion across the blood brain barrier, or astrocytic uptake through either phagocytosis or receptor-mediated endocytosis, where LRP1 has been well studied. Aβ bound to ApoE and high-density lipoproteins can also be cleared through microglial uptake or microglial-mediated neuroinflammatory responses. Mutations to the APOE gene are critically associated with late-onset Alzheimer’s disease; in this context, it is thought that altered ApoE function leads to extracellular Aβ aggregation and compromised integrity of neuronal membranes, which in turn prompts a neuroinflammatory response that further dysregulates the system. Despite its well-established association with the majority of non-familial AD cases, the mechanistic underpinnings of the pathogenic role of ApoE remain unclear.

Selected Reviews:

created December 2021
Acetylase
Acetylase
Metabolic Enzyme
Metabolic Enzyme
Adaptor
Adaptor
Methyltransferase or G-protein
Methyltransferase or G-protein
Adaptor
Apoptosis/Autophagy Regulator
Phosphatase
Phosphatase
Cell Cycle Regulator
Cell Cycle Regulator
Protein Complex
Protein Complex
Deacetylase or Cytoskeletal Protein
Deacetylase or Cytoskeletal Protein
Ubiquitin/SUMO Ligase or Deubiquitinase
Ubiquitin/SUMO Ligase or Deubiquitinase
Growth Factor/Cytokine/Development Protein
Growth Factor/Cytokine/Development Protein
Transcription Factor or Translation Factor
Transcription Factor or Translation Factor
GTPase/GAP/GEF
GTPase/GAP/GEF
Receptor
Receptor
Kinase
Kinase
Other
Other
 
Direct Process
Direct Process
Tentative Process
Tentative Process
Translocation Process
Translocation Process
Stimulatory Modification
Stimulatory Modification
Inhibitory Modification
Inhibitory Modification
Transcriptional Modification
Transcriptional Modification