Emerging biophysical techniques for probing synaptic transmission in neurodegenerative disorders

Neuroscience. 2024 Nov 26:565:63-79. doi: 10.1016/j.neuroscience.2024.11.055. Online ahead of print.

Abstract

Plethora of research has shed light on the critical role of synaptic dysfunction in various neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Synapses, the fundamental units for neural communication in the brain, are highly vulnerable to pathological conditions and are central to the progression of neurological diseases. The presynaptic terminal, a key component of synapses responsible for neurotransmitter release and synaptic communication, undergoes structural and functional alterations in these disorders. Understanding synaptic transmission abnormalities is crucial for unravelling the pathophysiological mechanisms underlying neurodegeneration. In the quest to probe synaptic transmission in NDDs, emerging biophysical techniques play a pivotal role. These advanced methods offer insights into the structural and functional changes occurring at nerve terminals in conditions like AD, PD, HD & ALS. By investigating synaptic plasticity and alterations in neurotransmitter release dynamics, researchers can uncover valuable information about disease progression and potential therapeutic targets. The review articles highlighted provide a comprehensive overview of how synaptic vulnerability and pathology are shared mechanisms across a spectrum of neurological disorders. In major neurodegenerative diseases, synaptic dysfunction is a common thread linking these conditions. The intricate molecular machinery involved in neurotransmitter release, synaptic vesicle dynamics, and presynaptic protein regulation are key areas of focus for understanding synaptic alterations in neurodegenerative diseases.

Keywords: AD; ALS; HD; Motor neurons; Optogenetics; PD; Synaptic transmission.

Publication types

  • Review