Neurodegenerative Disease: What Potential Therapeutic Role of Acid-Sensing Ion Channels?

Dalila Mango,Robert Nisticò

doi:10.3389/fncel.2021.730641

Abstract

Acidic pH shift occurs in many physiological neuronal activities such as synaptic transmission and synaptic plasticity but also represents a characteristic feature of many pathological conditions including inflammation and ischemia. Neuroinflammation is a complex process that occurs in various neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and Huntington’s disease. Acid-sensing ion channels (ASICs) represent a widely expressed pH sensor in the brain that play a key role in neuroinflammation. On this basis, acid-sensing ion channel blockers are able to exert neuroprotective effects in different neurodegenerative diseases. In this review, we discuss the multifaceted roles of ASICs in brain physiology and pathology and highlight ASIC1a as a potential pharmacological target in neurodegenerative diseases.

Highlights

Frontiers in Cellular NeurosciencePotential Therapeutic Role of Acid-Sensing Ion Channels? Front. Cell
The maintenance of cytosolic pH in its physiological range is required for normal neuronal activity, and even minor alterations can have serious consequences
Neurodegenerative diseases are characterized by different and multifactorial processes sharing accumulation of misfolding proteins, damage of specific neuronal populations, and chronic inflammation state neuroinflammation. Another common feature is the shift to the acidic pH in the brain, which might contribute to apoptosis, protein misfolding, excitotoxicity, and neurodegeneration (Parton et al, 1991; Bender et al, 1997; Ding et al, 2000; Liu et al, 2012; Wang et al, 2012)

Summary

Frontiers in Cellular Neuroscience

Potential Therapeutic Role of Acid-Sensing Ion Channels? Front. Cell. Potential Therapeutic Role of Acid-Sensing Ion Channels? Acidic pH shift occurs in many physiological neuronal activities such as synaptic transmission and synaptic plasticity and represents a characteristic feature of many pathological conditions including inflammation and ischemia. Neuroinflammation is a complex process that occurs in various neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and Huntington’s disease. Acid-sensing ion channels (ASICs) represent a widely expressed pH sensor in the brain that play a key role in neuroinflammation. On this basis, acid-sensing ion channel blockers are able to exert neuroprotective effects in different neurodegenerative diseases. We discuss the multifaceted roles of ASICs in brain physiology and pathology and highlight ASIC1a as a potential pharmacological target in neurodegenerative diseases

INTRODUCTION

NEUROINFLAMMATION PROCESS AND pH SHIFT IN NEURODEGENERATIVE DISORDERS

Multiple Sclerosis

Small Molecules

CONCLUSION