Alpha-Synuclein in bio fluids and tissues as a potential biomarker for Parkinson’s disease

Abstract

Background: Parkinson's disease (PD) is a chronic neurological disorder that impairs normal motor function and has no cure at present. Diagnosis of PD is clinical only; biopsies confirming the presence of the disease can only be done post-mortem. Furthermore, similarities in the manifestation of PD symptoms to other diseases such as Multiple System Atrophy (MSA), make early diagnosis difficult and ambiguous. As a result, there is a high demand for research investigating biomarkers for timely diagnosis of PD. Alpha-synuclein (α-SYN) is a protein found misfolded in the brain and other body tissues of PD patients. Its relevance and association to PD make it a prime biomarker candidate. However, reports in the literature suggest that the structural form and location of α-SYN are key to yield a reliable diagnosis. The aim of this Minireview is to highlight efforts made in studying α-SYN as a biomarker over the past decade. Key Findings: Based on the literature surveyed, α-SYN was indeed the most widely studied candidate biomarker for PD. Cerebrospinal fluid (CSF) and skin were promising sites for assessing α-SYN effectiveness in differentiating PD from MSA. Furthermore, gastro-intestinal α-SYN was suitable for early diagnosis of PD. A combination of total α-SYN and other forms including but not limited to phosphorylated α-SYN were the best predictors of the disease. Conclusion: Misdiagnosis of patients enrolled in clinical trials is a confounding factor for PD drug development. A robust biomarker for PD will help eradicate this problem. Identifying an accurate biomarker for PD will also ensure timely therapeutic intervention to manage symptoms better and improve the quality of life of patients. The promise α-SYN and its phosphorylated form show in different tissues is a step forward in this direction.