Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease

Abstract

Parkinson’s disease is the second most prevalent neurological disease after Alzheimer’s. Primarily, old age males are more affected than females. The aggregates of oligomeric forms of α-synuclein cause the loss of dopaminergic neurons in the substantia nigra pars compacta. Further, it leads to dopamine shortage in the striatum region. According to recent preclinical studies, environmental factors like pesticides, food supplements, pathogens, etc. enter the body through the mouth or nose and ultimately reach the gut. Further, these factors get accumulated in enteric nervous system which leads to misfolding of α-synuclein gene, and aggregation of this gene results in Lewy pathology in the gut and reaches to the brain through the vagus nerve. This evidence showed a strong bidirectional connection between the gut and the brain, which leads to gastrointestinal problems in Parkinson patients. Moreover, several studies reveal that patients with Parkinson experience more gastrointestinal issues in the early stages of the disease, such as constipation, increased motility, gut inflammation, etc. This review article focuses on the transmission of α-synuclein and the mechanisms involved in the link between the gut and the brain in Parkinson’s disease. Also, this review explores the various pathways involved in Parkinson and current therapeutic approaches for the improvement of Parkinson’s disease.