Mitochondrial metabolism: a common link between neuroinflammation and neurodegeneration

Abstract

Neurodegenerative disorders have been considered as a growing health concern for decades. Increasing risk of neurodegenerative disorders creates a socioeconomic burden to both patients and care givers. Mitochondria are organelle that are involved in both neuroinflammation and neurodegeneration. There are few reports on the effect of mitochondrial metabolism on the progress of neurodegeneration and neuroinflammation. Therefore, the present review summarizes the potential contribution of mitochondrial metabolic pathways in the pathogenesis of neuroinflammation and neurodegeneration. Mitochondrial pyruvate metabolism plays a critical role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. However, there its potential contribution in other neurodegenerative disorders is as yet unproven. The mitochondrial pyruvate carrier and pyruvate dehydrogenase can modulate mitochondrial pyruvate metabolism to attenuate neuroinflammation and neurodegeneration. Further, it has been observed that the mitochondrial citric acid cycle can regulate the pathogenesis of neuroinflammation and neurodegeneration. Additional research should be undertaken to target tricarboxylic acid cycle enzymes to minimize the progress of neuroinflammation and neurodegeneration. It has also been observed that the mitochondrial urea cycle can potentially contribute to the progression of neurodegenerative disorders. Therefore, targeting this pathway may control the mitochondrial dysfunction-induced neuroinflammation and neurodegeneration. Furthermore, the mitochondrial malate-aspartate shuttle could be another target to control mitochondrial dysfunction-induced neuroinflammation and neurodegeneration in neurodegenerative disorders.

Transcriptional Analysis of Nuclear-Encoded Mitochondrial Genes in Eight Neurodegenerative Disorders: The Analysis of Seven Diseases in Reference to Friedreich’s Ataxia

“…M, module; C, confidence. also reported that the mitochondrial citric acid cycle can regulate the pathogenesis of neuroinflammation and neurodegeneration (Garabadu et al, 2019). The identified genes that play a role in one or more of these pathways included COX6C, UQCRB, and NDUFA5.…”

Cognitive Impairment in Parkinson’s Disease: Epidemiology, Clinical Profile, Protective and Risk Factors

“…Inflammatory markers, including C-reactive protein [ 120 ] and IL-6 [ 75 ] and oxidative stress markers nitric oxide and hydroxyl radical have been found to be elevated in the CSF of patients with PD-MCI and correlate with lower MoCA scores [ 75 ]. Mitochondrial dysfunction can lead to an increase in oxidative stress as well as glial and astrocyte dysfunction, contributing to an abnormal inflammatory response [ 121 , 122 , 123 ]. In PDD, deficiency in mitochondrial complex 1 activity and reduced mitochondrial DNA levels in the prefrontal cortex, compared to healthy controls, have been described [ 124 ].…”

Inflammation-Related Changes in Mood Disorders and the Immunomodulatory Role of Lithium

“…Mitochondria are intracellular organelles that regulate energy metabolism, the production of reactive oxygen species (ROS), cellular signaling, Ca 2+ homeostasis, and apoptosis. Studies revealed that the mitochondrial dysfunction and damage play a crucial role in the development of neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease or multiple sclerosis, by enhancing innate and adaptive immune responses that result in neuroinflammation [55]. The dysfunction of mitochondria and impaired energy metabolism were also reported in the pathophysiology of mood disorders such as bipolar disorder and major depressive disorder [56][57][58][59].…”