α-synuclein Pathology and Treatment in the Enteric Nervous System

Abstract

\(\alpha\)-synuclein (Lewy Body) pathology is commonly found in the enteric nervous system (ENS) of patients diagnosed with Neurocognitive Disorder with Lewy Bodies (NCDLB) and Parkinson’s Disease (PD). Lewy body pathology in the ENS can produce symptoms of bowel immotility, including constipation, obstipation, and bowel impaction. The specific mechanism through which \(\alpha\)-synuclein (Lewy Body) pathology impairs bowel function is explained. These symptoms significantly reduce the quality of life for the patient, producing hardship for the patient and care providers. Hypothetically, medical intervention using acetylcholinesterase inhibitors (AChEIs) can significantly reduce or alleviate bowel immotility in Lewy body patients. The rationale for the use of the cholinergic agonist Donepezil to alleviate \(\alpha\)-synuclein bowel impairment is explained, including a description of its mechanism of action. Longitudinal case studies are described in which the hypothesis that AChEIs can mitigate Lewy Body-induced bowel immotility was tested. Over a five-year period, Donepezil demonstrated efficacy for mitigating bowel impairment in Lewy body patients.