New insight on microglia activation in neurodegenerative diseases and therapeutics

Abstract

Microglia are immune cells within the central nervous system (CNS) closely linked to brain health and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In response to changes in the surrounding environment, microglia activate and change their state and function. Several factors, example for circadian rhythm disruption and the development of neurodegenerative diseases, influence microglia activation. In this review, we explore microglia’s function and the associated neural mechanisms. We elucidate that circadian rhythms are essential factors influencing microglia activation and function. Circadian rhythm disruption affects microglia activation and, consequently, neurodegenerative diseases. In addition, we found that abnormal microglia activation is a common feature of neurodegenerative diseases and an essential factor of disease development. Here we highlight the importance of microglia activation in neurodegenerative diseases. Targeting microglia for neurodegenerative disease treatment is a promising direction. We introduce the progress of methods targeting microglia for the treatment of neurodegenerative diseases and summarize the progress of drugs developed with microglia as targets, hoping to provide new ideas for treating neurodegenerative diseases.

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

“…In neurodegenerative diseases, microglial activation involves cellular metabolism dysregulation and mitochondrial damage, leading to the accumulation of reactive oxygen species (ROS), amino acids, iron, ferroptosis, and eventual inflammation and cell death [ 66 , 85 , 86 , 87 ]. Recently, it was revealed that circadian rhythm also plays a critical role in microglia activation and function and that the disruption of this rhythm can lead to neurodegenerative diseases [ 88 ].…”

“…Synucleinopathies are also considered a hallmark of dementia, including PD dementia (PDD) and Lewy body dementia (LBD), where the latter comprises roughly 20–30% of all dementia cases in the world and is considered the third most common form of dementia [ 88 , 89 ]. In Alzheimer’s disease (AD), co-morbid α-Syn pathology is present in up to 50% of cases.…”

“…The cell-to-cell transmission of α-Syn aligns well with the clinical course of the disease and is now considered the underlying mechanism for neurodegenerative diseases. What may cause α-Syn misfolding in the first place is believed to involve a combination of factors, including aging, environmental factors, and exposure to toxins, which ultimately overwhelms the microglia’s ability to maintain homeostasis and leads to neurodegeneration [ 88 , 89 ]. Aberrant circadian rhythmicity may also lead to extensive α-Syn aggregation [ 90 ].…”

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

“…In neurodegenerative diseases, microglial activation involves cellular metabolism dysregulation and mitochondrial damage, leading to accumulation of reactive oxygen species (ROS), amino acids, iron, ferroptosis and eventual inflammation and cell death [66,[85][86][87]. Recently, it was revealed that the circadian rhythm also plays a critical role in microglia activation and function and that disruption of this rhythm can lead to neurodegenerative diseases [88].…”

“…Cell-to-cell transmission of α-Syn aligns well with the clinical course of the disease and is now considered the underlying mechanism for neurodegenerative diseases. What may cause α-Syn misfolding in the first place is believed to involve a combination of factors including aging, environmental factors, and exposure to toxins, which ultimately overwhelms the microglia's ability to maintain homeostasis and leads to neurodegeneration [88,89]. Aberrant circadian rhythmicity may also lead to extensive α-Syn aggregation [90].…”