Regulators of proteostasis are translationally repressed in fibroblasts from patients with sporadic and LRRK2-G2019S Parkinson's disease

Flinkman, Dani (author): Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,University of Turku,Åbo Akademi University

Peltonen, Sirkku, 1964 (author): University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för dermatologi och venereologi,Institute of Clinical Sciences, Department of Dermatology and Venereology,Sahlgrenska University Hospital,University of Turku,Turku University Hospital

James, Peter (author): Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,Åbo Akademi University,University of Turku

(creator_code:org_t)

2023-02-06
2023
English.
In: Npj Parkinsons Disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 9:1

Related links:: http://dx.doi.org/10... (free); show more...; https://gup.ub.gu.se...; https://doi.org/10.1...; https://lup.lub.lu.s...; show less...

Abstract Subject headings

Deficits in protein synthesis are associated with Parkinson's disease (PD). However, it is not known which proteins are affected or if there are synthesis differences between patients with sporadic and Leucine-Rich Repeat Kinase 2 (LRRK2) G2019S PD, the most common monogenic form. Here we used bio-orthogonal non-canonical amino acid tagging for global analysis of newly translated proteins in fibroblasts from sporadic and LRKK2-G2019S patients. Quantitative proteomic analysis revealed that several nascent proteins were reduced in PD samples compared to healthy without any significant change in mRNA levels. Using targeted proteomics, we validated which of these proteins remained dysregulated at the static proteome level and found that regulators of endo-lysosomal sorting, mRNA processing and components of the translation machinery remained low. These proteins included autophagy-related protein 9A (ATG9A) and translational stability regulator YTH N6-ethyladenosine RNA binding protein 3 (YTHDF3). Notably, 77% of the affected proteins in sporadic patients were also repressed in LRRK2-G2019S patients (False discovery rate (FDR) < 0.05) in both sporadic and LRRK2-G2019S samples. This analysis of nascent proteomes from PD patient skin cells reveals that regulators of proteostasis are repressed in both sporadic and LRRK2-G2019S PD.

By the author/editor: Flinkman, Dani; Hong, Y.; Gnjatovic, J.; Deshpande, P.; Ortutay, Z.; Peltonen, Sirkku ...; show more...; Kaasinen, V.; James, Peter; Coffey, E.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.