Autophagy-lysosome pathway as a source of candidate biomarkers for Parkinson’s disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1% of the worldwide population. Diagnosis of PD relies on clinical history and physical examination, but misdiagnosis is common in early stages. Despite considerable progress in understanding PD pathophysiology, including genetic and biochemical causes, diagnostic approaches lack accuracy and interventions are restricted to symptomatic treatments. Identification of biomarkers for PD may allow early and more precise diagnosis and monitoring of dopamine replacement strategies and disease-modifying treatments. Increasing evidence suggests that autophagic dysregulation causes the accumulation of abnormal proteins, such as aberrant α-synuclein, a protein critical to PD pathogenesis. Mutations in the GBA gene are a major PD risk factor and β-glucocerebrosidase (GCase) is also emerging as an important molecule in PD pathogenesis. Consequently, proteins involved in the autophagy-lysosome pathway and GCase protein levels and activity are prime targets for the research and development of new PD biomarkers. The studies so far in PD biological material have yielded some consistent results, particularly regarding the levels of Hsc70, a component of the chaperonemediated autophagy pathway, and the enzymatic activity of GCase in GBA mutation carriers. In the future, larger longitudinal studies, corroborating previous research on possible biomarker candidates, as well as extending the search for possible candidates for other lysosomal components, may yield more definitive results.