Paper
- Alzforum Recommends
Yao J, Du H, Yan S, Fang F, Wang C, Lue LF, Guo L, Chen D, Stern DM, Gunn Moore FJ, Xi Chen J, Arancio O, Yan SS. Inhibition of amyloid-beta (Abeta) peptide-binding alcohol dehydrogenase-Abeta interaction reduces Abeta accumulation and improves mitochondrial function in a mouse model of Alzheimer's disease. J Neurosci. 2011 Feb 9;31(6):2313-20. PubMed.
Recommends
Please login to recommend the paper.
Comments
University of Kansas
In this paper, the Yan lab does a remarkable job following up on its seminal 2004 work that showed Aβ and an alcohol dehydrogenase associate within the mitochondria of mutant APP transgenic mice. The findings in this current paper reinforce the view that a mitochondrial-Aβ nexus is functionally important, at least in these mice. The authors extend the original finding to further make the point that mitochondrial mechanisms, such as the PreP protein, may have evolved to regulate mitochondrial Aβ levels and dynamics. In the process, the authors have developed a potentially new and novel AD therapeutic, and made a good case for testing their novel therapeutic approach in humans. It's not everyday you encounter what is essentially basic research that has such obvious translational implications.
Weill Cornell Medical College
This is an impressive amount of work done by Dr. Yan and colleagues. The results strongly implicate a critical role for Aβ in mitochondria for AD pathogenesis. The finding that blocking the interaction of Aβ with Aβ peptide-binding alcohol dehydrogenase also leads to a reduction in Aβ levels due to degradation by PreP is also intriguing. The use of the reverse decoy peptide is an excellent control. The paper is also of interest in that it shows a means of getting peptides into brain mitochondria following systemic administration using a Tat peptide and a mitochondrial targeting sequence. It would be of interest to see if a similar approach would have efficacy in other species like aged primates, and whether tau pathology can be prevented using this approach.
Make a Comment
To make a comment you must login or register.