Altered Expression of DJ-1 and PINK1 in Sporadic ALS and in the SOD1(G93A) ALS Mouse Model

作者：Knippenberg Sarah^*; Sipos Julia; Thau Habermann Nadine; Koerner Sonja; Rath Klaus Jan; Dengler Reinhard; Petri Susanne

来源：Journal of Neuropathology and Experimental Neurology, 2013, 72(11): 1052-1061.

DOI：10.1097/NEN.0000000000000004

• Amyotrophic lateral sclerosis
• DJ-1
• mRNA expression
• PINK1
• SOD1(G93A) mouse model
• Sporadic ALS

Mitochondrial dysfunction is an important mechanism in the pathogenesis of neurodegenerative diseases such as Parkinson disease and amyotrophic lateral sclerosis (ALS). DJ-1 and PTEN-induced putative kinase 1 (PINK1) are important proteins for the maintenance of mitochondrial function and protection against cell death. Mutations in the genes coding for these proteins cause familial forms of Parkinson disease. Recent studies have postulated that changes in the expression of both proteins are also involved in pathologic mechanisms in ALS mouse models. Here, we studied the mRNA and protein expression of PINK1 and DJ-1 in postmortembrain and spinal cord tissue andmuscle biopsy samples from ALS patients and controls and in brain, spinal cord, and gastrocnemius muscle of SOD1(G93A) ALS mice at different disease stages. We found significant decreases of PINK1 and DJ-1 mRNA levels in muscle tissue of SOD1(G93A) mice. Together with the significant decrease of PINK1 mRNA levels in human ALS muscle tissue, statistically nonsignificant reduction of DJ-1 mRNA levels, and reduced immunostaining for PINK1 in human ALS muscle, the results suggest potential pathophysiologic roles for these proteins in both mutant SOD1(G93A) transgenic mice and in sporadic ALS.

• 出版日期2013-11