{Reference Type}: Journal Article
{Title}: A Mutual Nexus Between Epilepsy and α-Synuclein: A Puzzle Pathway.
{Author}: Ali NH;Al-Kuraishy HM;Al-Gareeb AI;Alnaaim SA;Hetta HF;Saad HM;Batiha GE;
{Journal}: Mol Neurobiol
{Volume}: 0
{Issue}: 0
{Year}: 2024 May 4
{Factor}: 5.682
{DOI}: 10.1007/s12035-024-04204-6
{Abstract}: Alpha-synuclein (α-Syn) is a specific neuronal protein that regulates neurotransmitter release and trafficking of synaptic vesicles. Exosome-associated α-Syn which is specific to the central nervous system (CNS) is involved in the pathogenesis of epilepsy. Therefore, this review aimed to elucidate the possible link between α-Syn and epilepsy, and how it affects the pathophysiology of epilepsy. A neurodegenerative protein such as α-Syn is implicated in the pathogenesis of epilepsy. Evidence from preclinical and clinical studies revealed that upregulation of α-Syn induces progressive neuronal dysfunctions through induction of oxidative stress, neuroinflammation, and inhibition of autophagy in a vicious cycle with subsequent development of severe epilepsy. In addition, accumulation of α-Syn in epilepsy could be secondary to the different cellular alterations including oxidative stress, neuroinflammation, reduction of brain-derived neurotrophic factor (BDNF) and progranulin (PGN), and failure of the autophagy pathway. However, the mechanism of α-Syn-induced-epileptogenesis is not well elucidated. Therefore, α-Syn could be a secondary consequence of epilepsy. Preclinical and clinical studies are warranted to confirm this causal relationship.