Scholarlink

<p>Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuron loss and α-synuclein aggregation. While some familial cases result from single-gene mutations, most are sporadic, involving complex genetic and environmental interactions. Among PD risk loci identified through genome-wide association studies, <i>MCCC1</i> encodes a mitochondrial enzyme essential for leucine catabolism; however, the causal variant remains unclear. Here, we investigated whether the intronic variant rs12637471 regulates <i>MCCC1</i> mRNA expression and influences PD risk. Postmortem brain analysis revealed significantly elevated <i>MCCC1</i> mRNA levels in G-allele carriers, consistent with peripheral tissue eQTL data from GTEx. Using CRISPR/Cas9-edited induced pluripotent stem cells, we generated isogenic lines differing only at rs12637471 and observed increased <i>MCCC1</i> expression in G-allele dopaminergic neurons. Given MCCC1’s mitochondrial role, its dysregulation may impact mitochondrial homeostasis, autophagy, or inflammation, potentially contributing to PD pathogenesis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Regulation of MCCC1 expression by a Parkinson’s disease-associated intronic variant: implications for pathogenesis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月11日

查看全文
  • Shunsaku Sogabe,
  • Hiroko Nakano,
  • Yusuke Ogasahara,
  • Pei-Chieng Cha,
  • Yuko Ando,
  • Mariko Taniguchi-Ikeda,
  • Ryusaku Matsumoto,
  • Motoi Kanagawa,
  • Kazuhiro Kobayashi,
  • Shigeo Murayama,
  • Takashi Aoi,
  • Tatsushi Toda,
  • Wataru Satake

摘要

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuron loss and α-synuclein aggregation. While some familial cases result from single-gene mutations, most are sporadic, involving complex genetic and environmental interactions. Among PD risk loci identified through genome-wide association studies, MCCC1 encodes a mitochondrial enzyme essential for leucine catabolism; however, the causal variant remains unclear. Here, we investigated whether the intronic variant rs12637471 regulates MCCC1 mRNA expression and influences PD risk. Postmortem brain analysis revealed significantly elevated MCCC1 mRNA levels in G-allele carriers, consistent with peripheral tissue eQTL data from GTEx. Using CRISPR/Cas9-edited induced pluripotent stem cells, we generated isogenic lines differing only at rs12637471 and observed increased MCCC1 expression in G-allele dopaminergic neurons. Given MCCC1’s mitochondrial role, its dysregulation may impact mitochondrial homeostasis, autophagy, or inflammation, potentially contributing to PD pathogenesis.