Autophagic signatures in peripheral blood mononuclear cells from Parkinson's disease patients

• Published in: Molecules and cells Vol. 48; no. 2; pp. 100173 - 14
• Main Authors: Lee, Myung Shin, Kim, Jae Whan, Park, Don Gueu, Heo, Hansol, Kim, Juyeong, Yoon, Jung Han, Chang, Jaerak
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2025; Korean Society for Molecular and Cellular Biology; 한국분자세포생물학회
• Subjects: Aged; Autophagy; Autophagy-lysosomal pathway; Biomarkers; Biomarkers - blood; Biomarkers - metabolism; Cell Cycle Proteins; Female; Humans; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Lysosomal-associated membrane protein 1; Lysosomes - metabolism; Male; Membrane Transport Proteins; Middle Aged; Optineurin; Parkinson Disease - blood; Parkinson Disease - diagnosis; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson’s disease; Transcription Factor TFIIIA - metabolism; 생물학; Biomarkers; Optineurin; Lysosomal-associated membrane protein 1; Parkinson’s disease; Autophagy-lysosomal pathway
• ISSN: 1016-8478; 0219-1032; 0219-1032
• DOI: 10.1016/j.mocell.2024.100173

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor impairments and the accumulation of misfolded α-synuclein. Dysregulation of the autophagy-lysosomal pathway (ALP), responsible for degrading misfolded proteins, has been implicated in PD pathogenesis. However, current diagnostic approaches rely heavily on motor symptoms, which occur due to substantial neurodegeneration, limiting early detection and intervention. This study investigated the potential of ALP-associated proteins in peripheral blood mononuclear cells (PBMCs) as diagnostic biomarkers for early-stage PD. Quantitative analysis revealed a significant reduction in optineurin levels in PBMCs from PD patients, and the expression levels of various ALP-associated proteins were tightly correlated, suggesting a coordinated dysregulation of the pathway. Correlation analyses revealed associations between ALP-associated features and clinical characteristics, such as age of onset and motor impairment. Furthermore, the study identified multiple positive correlations among ALP-associated proteins and functional readouts, highlighting the interconnectivity within the pathway. Notably, a PBMC biomarker model incorporating lysosomal-associated membrane protein 1 and optineurin exhibited high diagnostic accuracy (86%) in distinguishing PD patients from controls. These findings highlight the potential of ALP-associated protein signatures in PBMCs as novel diagnostic biomarkers for early detection and intervention in PD, offering insights into the systemic manifestations of the disease.