Synapse loss is an early feature shared by many neurodegenerative diseases, and it represents the major correlate of cognitive impairment. Recent studies reveal that microglia and astrocytes play a major role in synapse elimination, contributing to network dysfunction associated with neurodegeneration. Excitatory and inhibitory activity can be affected by glia-mediated synapse loss, resulting in imbalanced synaptic transmission and subsequent synaptic dysfunction. Here, we review the recent literature on the contribution of glia to excitatory/inhibitory imbalance, in the context of the most common neurodegenerative disorders. A better understanding of the mechanisms underlying pathological synapse loss will be instrumental to design targeted therapeutic interventions, taking in account the emerging roles of microglia and astrocytes in synapse remodeling.
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http://dx.doi.org/10.3389/fncel.2019.00063 | DOI Listing |
Background: Bridge-like lipid transfer proteins (BLTPs) mediate bulk lipid transport at membrane contact sites. Mutations in BLTPs are linked to both early-onset neurodevelopmental and later-onset neurodegenerative diseases, including movement disorders. The tissue specificity and temporal requirements of BLTPs in disease pathogenesis remain poorly understood.
View Article and Find Full Text PDFElectroencephalographic (EEG) recordings in individuals with Fragile X Syndrome (FXS) and the mouse model of FXS ( KO) display cortical hyperexcitability at rest, as well as deficits in sensory-driven cortical network synchrony. A form of circuit hyperexcitability is observed in cortical slices of KO mice as prolonged persistent activity, or Up, states. It is unknown if the circuit mechanisms that cause prolonged Up states contribute to FXS-relevant EEG phenotypes.
View Article and Find Full Text PDFJ Prev Alzheimers Dis
January 2025
School of Health and Biomedical Sciences, RMIT University, 220 3-5 Plenty Road, Bundoora VIC 3082, Australia. Electronic address:
Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized by the accumulation of toxic amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) of tau protein in the brain. Microglia, key immune cells of the central nervous system, play an important role in AD development and progression, primarily through their responses to Aβ and NFTs. Initially, microglia can clear Aβ, but in AD, chronic activation overwhelms protective mechanisms, leading to sustained neuroinflammation that enhances plaque toxicity, setting off a damaging cycle that affects neurons, astrocytes, cerebral vasculature, and other microglia.
View Article and Find Full Text PDFExp Eye Res
January 2025
Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. Electronic address:
Autophagy is common in the aging retinal pigment epithelium (RPE). A dysfunctional autophagy in aged RPE is implicated in the pathogenesis of age-related macular degeneration. Aging human retina accompanies degenerative changes in photoreceptor mitochondria.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Hefei National Laboratory for Physical Sciences at the Microscale, MOE Key Laboratory for Membrane-Less Organelles & Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.
Mitochondrial function is essential for synaptic function. ATAD1, an AAA+ protease involved in mitochondrial quality control, governs fission-fusion dynamics within the organelle. However, the distribution and functional role of ATAD1 in neurons remain poorly understood.
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