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A number of mutations that lead to familial PD have been linked to alterations in UPS function, including mutations in SNCA [226], UCHL1 227 , and PRKN [228]

Supplemental Figure 3: The effect of 4OI treatment on Acod1 expression levels upon Tat or Tat-Cocaine treatment (A) Acod1 expression level, normalized to counts per million reads, after 48h of Tat treatment, with or without 4OI, and with or without cocaine exposure for 24 h

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However, human epidemiological evidence for transgenerational effects remains limited, primarily due to the extended timeframes required for multigenerational studies and the practical challenges of maintaining long-term cohorts across decades ( Low-Dose Chronic Exposure Effects Present Assessment Challenges EEDs frequently exhibit non-monotonic dose-response (NMDR) patterns, where low-dose chronic exposure may produce more pronounced biological effects than acute high-dose exposure