Fig. 6

The dysfunction of mitochondrial-associated genes harms normal brain homeostasis by targeting the Oxidative phosphorylation mechanism that results in uncontrollable ROS generation. The activation of the Caspase cascade due to ROS helps produce pro-inflammatory markers that activate the resting microglia cells. The cytokines induce BBB damage by targeting the tight junction proteins and membrane integrity, causing cortical neuron death, cerebral ischemia, arrhythmia, epilepsy episodes, and also cognitive impairment. Lacampagne A et al.,⁴³ have reported Ryr with a causative linkage to Alzheimer’s disease. The leaky RyR2 has been considered as the “biochemical signature” and was associated with an ER Ca²⁺ leak, through increased RyR2 open probability and a loss of memory⁴³. For analysing and accessing the crucial role of the BBB proteins holding and maintaining its integrity, Table 2 has been shown below that signifies the importance of different tight junction proteins that helps in the maintenance of an isolated system enclosing the BBB. The primary goal of this research article is thus, to highlight and associate the leaky BBB during COVID infection could lead to prolonged cytokine storm and systemic inflammation thereby, triggering the brain cells to leverage a deleterious effect caused by oxidative stress that could damage a variety of cells such as BMVECs, pericytes, and astrocytes, destroying the BBB.