Journal of Alzheimers Disease & Parkinsonism
天美传媒 Access
Our Group organises 3000+ Global Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ 天美传媒 Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.
天美传媒 Access Journals gaining more Readers and Citations
700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers
Citations : 4334
Indexed In
- Index Copernicus
- Google Scholar
- Sherpa Romeo
- 天美传媒 J Gate
- Genamics JournalSeek
- Academic Keys
- JournalTOCs
- China National Knowledge Infrastructure (CNKI)
- Electronic Journals Library
- RefSeek
- Hamdard University
- EBSCO A-Z
- OCLC- WorldCat
- SWB online catalog
- Virtual Library of Biology (vifabio)
- Publons
- Geneva Foundation for Medical Education and Research
- Euro Pub
- ICMJE
Useful Links
Recommended Journals
Related Subjects
Share This Page
Neuropathophysiology cross-talk between Alzheimer′s and Parkinson′s disease
11th International Conference on Alzheimers Disease & Dementia
Li Zeng, Zhongcan Chen, Wei Zhang, Ling Ling Chua, Chou Chai, Rong Li, Lin Lin, Zhen Cao, Dario C Angeles, Lawrence W Stanton, Jianhe Peng, Zhi Dong Zhou, Kah Leong Lim and Eng King Tan
National Neuroscience Institute, Singapore The Experimental Therapeutics Centre (ETC)-A*STAR, Singapore Genome Institute of Singapore (GIS)-A*STAR, Singapore National University of Singapore, ingapore 5DUKE-NUS Medical School, Singapore
ScientificTracks Abstracts: J Alzheimers Dis Parkinsonism
DOI:
Abstract
Background: Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of familial and sporadic Parkinson芒�?�?s disease (PD). Amyloid precursor protein (APP) is an important molecule in Alzheimer芒�?�?s disease (AD). Although recent research revealed that there might be common pathophysiological and genetic links between these two diseases, little is known about the potential biological interplay between LRRK2 and APP. Materials & Methods: Here, we used LRRK2 G2019S mouse models and induced pluripotent stem cell (iPSC)芒�?�?derived neurons from PD patients to investigate the potential pathophysiological interplay between LRRK2 and APP in PD. Results: We demonstrate here that LRRK2 interacts with APP and LC/MS/MS analysis revealed LRRK2 phosphorylates APP at threonine-668 (T668). This in turn stimulates the production of the APP intracellular domain (AICD) and enhances AICD nuclear translocation, which is associated with the dopaminergic neuron loss in aging LRRK2 G2019S mutant mice. Importantly, we found that the expression of AICD exacerbates LRRK2 G2019S-induced neurotoxicity, whereas phosphomutant AICD (T668A) has no effect on LRRK2 G2019S-induced neuronal loss in vitro and in LRRK2 G2019S mutant mice. Moreover, dopaminergic neurons generated from LRRK2 G2019S patient-derived induced pluripotent stem cells exhibit significantly elevated phospho-APP T668 levels relative to their counterparts derived from healthy individuals. The level of T668- phosphorylated APP is also significantly increased in LRRK2 G2019S post-mortem human brain tissues. Treatment with LRRK2 inhibitors reduces phosphorylation at T668 in LRRK2 G2019S patient芒�?�?s dopaminergic neurons and in LRRK2 G2019S mutant mice. Discussion: APP and LRRK2 are physically and functionally linked, suggesting a shared pathway between the two most common neurodegenerative diseases that may help explain their overlapping pathology, especially in advanced stages of the respective disease. Conclusions: APP is a substrate of LRRK2, and its phosphorylation promotes AICD function and neurotoxicity in PD.Biography
Li Zeng is currently working as Senior Research Scientist and Principal Investigator at Neural Stem Cells Research Laboratory at National Neuroscience Institute, Singapore. He has published more than 25 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Email:Li_Zeng@nni.com.sg
