Cell-Type Specific Mitochondrial Quality Control in the Brain: A Precise Mechanism of Neurodegeneration

Abstract

Neurodegeneration is an age-dependent progressive phenomenon with no defined cause. Aging is the main risk factor for neurodegenerative diseases. During aging, activated microglia undergoes phenotypic alterations that can lead to neuroinflammation, which is well accepted event in the pathogenesis of neurodegenerative diseases. Several common mechanisms are shared by genetically or pathologically distinct neurodegenerative diseases, such as excitotoxicity, mitochondrial deficits and oxidative stress, protein misfolding and translational dysfunction, autophagy and microglia activation. Progressive loss of neuronal population due to increased oxidative stress leads to neurodegenerative diseases mostly due to the accumulation of dysfunctional mitochondria. Mitochondrial dysfunction and excessive neuroinflammatory responses are both sufficient to induce pathology in age-dependent neurodegeneration. Therefore, mitochondrial quality control is key determinant for the health and survival of neuronal cells in the brain. Research has been primarily focused to demonstrate the significance of neuronal mitochondrial health, despite the important contributions of non-neuronal cells that constitutes significant portion of the brain volume. Moreover, mitochondrial morphology and function are distinctly diverse in different tissues; however, little is known about their molecular diversity among cell types. Mitochondrial dynamics and quality in different cell types markedly decides the fate of overall brain health, therefore it is not justifiable to overlook non-neuronal cells and their significant and active contribution in facilitating overall neuronal health. In this review article, we aim to discuss the mitochondrial quality control of different cell types in the brain and how important and remarkable is the diversity and highly synchronized connecting property of non-neuronal cells in keeping the neurons healthy to control neurodegeneration.

Microglia as a Possible Alternative Therapeutic for Dementia

“…Oligodendrocytes are myelinating brain cells that keep neurons healthy [15]. In addition to providing insulation to the axons, they provide trophic support, affect the structure of the axons, and modify their electrical properties by controlling their diameter and the grouping of specific ion channels in the nodal and paranodal region.…”

“…Astrocytes, which constitute about 20-40% of the brain cells, are the main secretory cells, they release gliotransmitters, including neurotransmitters. In an activated state, activated microglia and reactive astrocytes release soluble factors (glutamate, reactive oxygen species (ROS) and cytokines) that adversely influence neurons and trigger neuroinflammatory signals in them [15,16]. Due to their important neuroinflammatory activity, astrocytes are generally considered another important response to neurodegeneration [17].…”

“…In response to a pathogen, microglia act rapidly, acquiring different phenotypes to defend neurons. During neuroinflammation, reactive microglia and astrocytes secrete soluble mediators that negatively affect neuronal health and promote neurodegeneration [15].…”