Abstract
An emerging concept termed the “neuro-glia-vascular unit” (NGVU) has been established in recent years to understand the complicated mechanism of multicellular interactions among vascular cells, glial cells, and neurons. It has been proverbially reported that the NGVU is significantly associated with neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Physiological aging is an inevitable progression associated with oxidative damage, bioenergetic alterations, mitochondrial dysfunction, and neuroinflammation, which is partially similar to the pathology of AD. Thus, senescence is regarded as the background for the development of neurodegenerative diseases. With the exacerbation of global aging, senescence is an increasingly serious problem in the medical field. In this review, the coupling of each component, including neurons, glial cells, and vascular cells, in the NGVU is described in detail. Then, various mechanisms of age-dependent impairment in each part of the NGVU are discussed. Moreover, the potential bioenergetic alterations between different cell types in the NGVU are highlighted, which seems to be an emerging physiopathology associated with the aged brain. Bioenergetic intervention in the NGVU may be a new direction for studies on delaying or diminishing aging in the future.
Highlights
Aging is a complex and irreversible process characterized by a gradual loss of biological function and increased susceptibility to neurodegenerative diseases [1]
Recent studies have shown that physiological aging may lead to damage or dysfunction of neuro-glia-vascular unit (NGVU) components [12], which acts as a background for neurodegenerative diseases
Considering the close cooperation between each component in the NGVU, the damage caused by senescence is disastrous for the morphology and function [7] of neurons, glial cells, and vascular cells
Summary
Over the past few years, the concept of the NGVU has been proposed to understand the progression of cerebral ischemic injury and neurodegenerative diseases [13, 14]. This emerging concept highlighted the interactions among multiple cell types but did not focus on identifying the unique contribution of each cell type, which has revised the neuro-centric view of brain diseases. The NGVU plays a vital role in the production and development of the blood brain barrier (BBB) to maintain a stable environment for brain function [18, 19]
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