A Mutual Nexus Between Epilepsy and α-Synuclein: A Puzzle Pathway.
Naif H AliHayder M Al-KuraishyAli I Al-GareebSaud A AlnaaimHelal F HettaHebatallah M SaadGaber El-Saber BatihaPublished in: Molecular neurobiology (2024)
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.
Keyphrases
- oxidative stress
- temporal lobe epilepsy
- traumatic brain injury
- signaling pathway
- multiple sclerosis
- cell death
- diabetic rats
- endoplasmic reticulum stress
- cell proliferation
- cerebral ischemia
- dna damage
- early onset
- cell therapy
- lipopolysaccharide induced
- small molecule
- induced apoptosis
- blood brain barrier
- long non coding rna
- mesenchymal stem cells
- single cell