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Plasma ubiquitin C-terminal hydrolase L1 levels reflect disease stage and motor severity in Parkinson's disease. | LitMetric

AI Article Synopsis

  • - Parkinson's disease (PD) is marked by the presence of Lewy bodies with α-synuclein and ubiquitin aggregates, which may be linked to a breakdown in the ubiquitin proteasome system.
  • - The study measured plasma UCHL1 levels in 291 people, finding that those with moderate PD (H&Y stage >2) had significantly higher UCHL1 levels compared to those with milder PD and healthy controls.
  • - UCHL1 levels were found to correlate with motor function in PD patients, but not global cognition, suggesting its potential role in PD progression that needs further investigation in future studies.

Article Abstract

Parkinson's disease (PD) is characterized by Lewy bodies containing α-synuclein and ubiquitin aggregates, their co-occurrence possibly linked to a failure of the ubiquitin proteasome system. Ubiquitin C-terminal hydrolase L1 (UCHL1) plays an important role in maintenance of nervous system integrity, and overexpression of UCHL1 has been shown to increase ubiquitin levels within neurons. While cerebrospinal fluid ubiquitin levels were reported to be lower in PD vs controls, plasma UCHL1 levels and their relationship with clinical measures in PD has not been reported. We measured plasma UCHL1 levels using single molecule array (Simoa) in 291 subjects (242 PD and 49 healthy controls, HC). We found that UCHL1 levels were significantly higher in PD patients at moderate stages (Hoehn and Yahr, H&Y stage >2) vs milder PD (H&Y ≤2, <0.001) and HC (=0.001). There was no significant difference in UCHL1 levels between PD patients at H&Y stages ≤2 vs HC. Across all PD patients, UCHL1 correlated significantly with UPDRS Part III motor scores (=3.87, 95% CI=0.43-7.31, =0.028), but not with global cognition. Overall, we found that UCHL1 correlates with motor function in PD, with higher levels seen in later disease stages. These findings will be validated in longitudinal studies.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053593PMC
http://dx.doi.org/10.18632/aging.102695DOI Listing

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