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185 citations
Review
13 August 2019

Brain derived neurotrophic factor (BDNF) is well recognized for its neuroprotective functions, via activation of its high affinity receptor, tropomysin related kinase B (TrkB). In addition, BDNF/TrkB neuroprotective functions can also be elicited indirectly via activation of adenosine 2A receptors (A2aRs), which in turn transactivates TrkB. Evidence suggests that alterations in BDNF/TrkB, including TrkB transactivation by A2aRs, can occur in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Although enhancing BDNF has been a major goal for protection of dying motor neurons (MNs), this has not been successful. Indeed, there is emerging in vitro and in vivo evidence suggesting that an upregulation of BDNF/TrkB can cause detrimental effects on MNs, making them more vulnerable to pathophysiological insults. For example, in ALS, early synaptic hyper-excitability of MNs is thought to enhance BDNF-mediated signaling, thereby causing glutamate excitotoxicity, and ultimately MN death. Moreover, direct inhibition of TrkB and A2aRs has been shown to protect MNs from these pathophysiological insults, suggesting that modulation of BDNF/TrkB and/or A2aRs receptors may be important in early disease pathogenesis in ALS. This review highlights the relevance of pathophysiological actions of BDNF/TrkB under certain circumstances, so that manipulation of BDNF/TrkB and A2aRs may give rise to alternate neuroprotective therapeutic strategies in the treatment of neural diseases such as ALS.

29,220 views
107 citations
Pathophysiology of multiple sclerosis (MS). While myelin loss is a central feature of MS pathology, it is accompanied by neurodegeneration, gliosis and immune cell (B-cells and T-cells) infiltration. Release of pro-inflammatory mediators and disrupted glutamate handling by glial cells leads to a toxic neuronal milieu. Furthermore, there is evidence that microglia are involved in complement-dependent synapse engulfment.
Review
26 February 2019
Glial Contribution to Excitatory and Inhibitory Synapse Loss in Neurodegeneration
Christopher M. Henstridge
1 more and 
Rosa C. Paolicelli

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.

26,723 views
110 citations
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Frontiers in Molecular Neuroscience

Synaptic Transmission with a Focus on Neural Networks of Alzheimer's Disease
Edited by Dongyu Wei, Mahima Sharma, Ana Garcia-Osta, Jose H Ledo
Deadline
06 January 2025
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