COVID‐19 and neurodegeneration: The mitochondrial connection

Abstract

There is still a significant lack of knowledge regarding many aspects of the etiopathology and consequences of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in humans. For example, the variety of molecular mechanisms mediating this infection, and the long‐term consequences of the disease remain poorly understood. It first seemed like the SARS‐CoV‐2 infection primarily caused a serious respiratory syndrome. However, over the last years, an increasing number of studies also pointed towards the damaging effects of this infection has on the central nervous system (CNS). In fact, evidence suggests a possible disruption of the blood–brain barrier and deleterious effects on the CNS, especially in patients who already suffer from other pathologies, such as neurodegenerative disorders. The molecular mechanisms behind these effects on the CNS could involve the dysregulation of mitochondrial physiology, a well‐known early marker of neurodegeneration and a hallmark of aging. Moreover, mitochondria are involved in the activation of the inflammatory response, which has also been broadly described in the CNS in COVID‐19. Here, we critically review the current bibliography regarding the presence of neurodegenerative symptoms in COVID‐19 patients, with a special emphasis on the mitochondrial mechanisms of these disorders.

Deep Learning Behavioral Phenotyping System in the Diagnosis of Parkinson’s Disease with Drosophila melanogaster

“…Not only PD cause a great burden of patients, but also lead to a significant increase in the risk of suicide 17 . Actually, the pandemic of Covid-19 also has a severe impact on the central nervous system, such as disrupting the blood brain barrier 18 . The spread of Covid-19 also challenges the prevention and the hospitalized management of PD patients 19,20 .…”

COVID-19 related neurological manifestations in Parkinson’s disease: has ferroptosis been a suspect?

“…Although endoplasmic reticulum-resident selenoproteins are known to have a role in preserving endoplasmic reticulum homeostasis, a connection between coronavirus infection and endoplasmic reticulum-resident selenoproteins has not yet been established [ 74 ]. Moreover, mitochondria have a role in the induction of the inflammatory response, including the production of mitochondrial reactive oxygen species(ROS) and the up-regulation of the expression of genes linked to glycolysis-related enzymes, which has also been extensively reported in the CNS in COVID-19 [ 75 ]. Dysregulation of the mitochondrial ACE2/MrgE/NO axis may have a significant effect on the neurodegenerative processes of dopaminergic neurons, where mitochondrial dysfunction and oxidative stress may have a substantial impact [ 76 ].…”

Effect of physical activity on long COVID fatigue: an unsolved enigma

“…One hypothesis is based on the observation of the deleterious effects of this infection on the central nervous system, especially in subjects already suffering from other debilitating conditions such as neurodegenerative diseases. 27 In particular, it has recently been hypothesised that neuronal damage could be due to a dysregulation of mitochondrial function, which is not only an early marker of neurodegenerative processes but also, more generally, a specific sign of general ageing, 28 also because mitochondria are involved in the activation of the inflammatory response. 28 Given that mitochondria must be involved in the phenomenon of muscle fatigue, this organelle becomes a potential target for understanding at least some of the molecular mechanisms underlying the cellular changes induced by the binding of Spike protein of SARS-CoV-2 to angiotensin I converting enzyme 2 (ACE-2).…”

“…27 In particular, it has recently been hypothesised that neuronal damage could be due to a dysregulation of mitochondrial function, which is not only an early marker of neurodegenerative processes but also, more generally, a specific sign of general ageing, 28 also because mitochondria are involved in the activation of the inflammatory response. 28 Given that mitochondria must be involved in the phenomenon of muscle fatigue, this organelle becomes a potential target for understanding at least some of the molecular mechanisms underlying the cellular changes induced by the binding of Spike protein of SARS-CoV-2 to angiotensin I converting enzyme 2 (ACE-2). The Physiological Society (UK) organised a virtual meeting in February 2022, the results of which were published in January 2023.…”