Elevated peripheral levels of receptor-interacting protein kinase 1(RIPK1)and IL-8 as biomarkers of human amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS)is a devastating fatal neurodegenerative disease with no cure.Receptor-interacting protein kinase 1(RIPK1)has been proposed to mediate pathogenesis of ALS.Primidone has been identified as an old drug that can also inhibit RIPK1 kinase.We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS patients.SOD1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor performance.One-hundred-sixty-two ALS participants dosed daily with primidone(62.5 mg)completed 24-week follow-up.A significant reduction was showed in serum levels of RIPK1 and IL-8,which were significantly higher in ALS patients than that of healthy controls(P<0.0001).Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms(P<0.05).Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS patients.Repurposing primidone may provide a promising therapeutic strategy for ALS.The effect of primidone for the treatment of other inflammatory diseases may also be considered,since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome(CRS).(ChiCTR2200060149).

Correction to:PINK1 mediates neuronal survival in monkey

CORRECTION TO:PROTEIN CELL HTTPS://DOI.ORG/10.1007/S13238-021-00889-W In the Original version of the article,the first two author names were incorrect.The Correct names are given below:Ziyu Sun,Jianyu Ye.OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article's Creative Commons licence.

PINK1 mediates neuronal survival in monkey

Parkinson's disease(PD)is one of the most common neu-rodegenerative diseases with progressive motor dysfunction and pathologically characterized by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain and the development of neuronal Lewy bodies.Autosomal recessive mutations in the gene PINK1 leads to inherited idiopathic PD.PINK1 is known to regulate PARKIN translocation upon mitochondrial damage which drives their removal via selective autophagy,a process known as mito-phagy(Pickrell and Youle 2015;Cummins and Gotz 2018).While mitochondrial defects had been noted in postmortem studies of patient brain samples with PD,there is a continuing debate as how mutations in PINK1 may lead to selective neuronal death in the substantia nigra.