Alternative Translation Initiation in <scp> <i>PRKN</i> </scp> Delays the Onset of Parkinson's Disease and Offers a Therapeutic Target
Residual truncated Parkin function provides a molecular explanation for a delayed disease onset in PRKN Exon 2 deletion carriers. Whereas this retained activity can be pharmacologically enhanced, the modulator's inhibitory effect on endogenous full-length Parkin may mandate strict patient stratification based on genotype. This finding offers mutation-specific counseling opportunities and highlights a potential therapeutic approach for appropriately selected patients with PARK-PRKN. ANN NEUROL 2026.
Authors
- Aleksandar Raković (ORCID: https://orcid.org/0000-0002-8127-7911)
- Suzanne Lesage
- Carolyn M. Sue (ORCID: https://orcid.org/0000-0003-1255-3617)
- Manabu Funayama
- Britta Meier
- Arian Hach (ORCID: https://orcid.org/0000-0002-7557-2391)
- Brice Alexis
- Hiroyo Yoshino (ORCID: https://orcid.org/0009-0002-6641-8728)
- Jean-Christophe Corvol
- Katja Lohmann
- Christine Klein
- Poornima J. Menon
- Nobutaka Hattori
- Eva‐Juliane Vollstedt
- Teresa Kleinz
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- RIKEN Center for Brain Science (JP)
- UNSW Sydney (AU)
- Juntendo University (JP)
- Sorbonne Université (FR)
- Institut du Cerveau (FR)
- Neuroscience Research Australia (AU)
- University of Lübeck (DE)
Publication Details
- Journal
- Annals of Neurology
- Published
- 2026-02-22
- DOI
- https://doi.org/10.1002/ana.78180
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- National Health and Medical Research Council