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TR-FRET-Based Immunoassay to Measure Ataxin-2 as a Target Engagement Marker in Spinocerebellar Ataxia Type 2
Mol Neurobiol. 2023 Mar 9. doi: 10.1007/s12035-023-03294-y. Online ahead of print.ABSTRACTSpinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disease, which belongs to the trinucleotide repeat disease group with a CAG repeat expansion in exon 1 of the ATXN2 gene resulting in an ataxin-2 protein with an expanded polyglutamine (polyQ)-stretch. The disease is late manifesting leading to early death. Today, therapeutic interventions to cure the disease or even to decelerate disease progression are not available yet. Furthermore, primary readout parameter for disease progression and thera...
Source: Molecular Medicine - March 9, 2023 Category: Molecular Biology Authors: Jessica Bux Nesli Ece Sen Isa-Maria Klink Stefan Hauser Matthis Synofzik Ludger Sch öls Georg Auburger Olaf Riess Jeannette H übener-Schmid Source Type: research

MutL homolog 1 contributes to temozolomide-induced autophagy via ataxia-telangiectasia mutated in glioma.
Abstract In the present study, mutL homolog 1 (MLH1) small interfering (si)RNA, KU‑55933, an ataxia‑telangiectasia mutated (ATM) inhibitor, and compound C, an adenosine monophosphate‑activated protein kinase (AMPK) inhibitor, were used to investigate the mechanisms underlying temozolomide (TMZ)‑induced autophagy and to determine the role of MLH1 and ATM in autophagy. MLH1 siRNA and KU‑55933 inhibited the phosphorylation of AMPK and ULK1 and reduced the levels of autophagy. MLH1 siRNA inhibited the phosphorylation of ATM and attenuated TMZ cytotoxicity, whereas the inhibition of ATM‑AMPK augmented TM...
Source: Molecular Medicine - February 3, 2015 Category: Molecular Biology Authors: Zou Y, Wang Q, Wang W Tags: Mol Med Rep Source Type: research