\nSecond year of a 2 year project
\nContact:
\n
![\"Dr.](\"https:\/\/arsacs.com\/wp-content\/uploads\/2021\/02\/watt-1-150x150-2.jpg\")
<\/p>\nAim 1 Identifying druggable Targets for potential ARSACS treatment
\nWe have recently identified that the endosomal Na+\/H+ exchanger NHE6, which is involved in regulating pH, is downregulated in anterior Purkinje cells of Sacs\uf02d\/\uf02d mice. Interestingly, these are the Purkinje cells that are more susceptible to cell death in ARSACS. Could the loss of NHE6 contribute to Purkinje cell death? Proper pH is essential for endosomal function, and changes result in erroneous trafficking of cargo. NHE6 results in overacidifcation of recycling endosomes which prevents the trafficking of cargo to the appropriate sites in neurons resulting in their dysfunction. For example, endosomal trafficking is important for controlled transport of glutamate receptors that mediate synaptic transmission, which we previously reported was altered in in Sacs-\/- mice. We will now restore endosome acidification and cargo mistrafficking in Sacs\uf02d\/\uf02d to see if this prevents synaptic deficits and cell loss. Additionally, we have evidence suggesting Mito-Q as a novel therapy to improve mitochondrial function, prevent cell loss, and improve cerebellar-related motor coordination in Sacs\uf02d\/\uf02d mice.<\/p>\n
Aim 2 Characterize pathophysiology for future druggable target development
\nWe continue to pursue the identification of novel druggable targets by understanding the pathophysiological alterations that give rise to dysfunction in Sacs\uf02d\/\uf02d mice. To this end, we are exploring whether changes in Purkinje cell firing, and\/or their innervation of downstream targets in the DCN, contribute to Purkinje cell loss and motor coordination deficits in in Sacs\uf02d\/\uf02d mice.<\/p>\n
Grant: $125,000
\nSecond year of a 2 year project
\nContact:
\n<\/p>\n
Dr. Alanna Watt,Department of Biology McGill University Bellini Life Sciences Bldg.
\n3469 Sir William Osler, Montreal, Quebec Canada H3G 0B1 Office: Rm. 265 | Lab: Rm. 257
\nTel: (514)-398-2806; Fax: (514)-398-5069; Email: alanna.watt@mcgill.ca<\/p>\n
![\"Dr.](\"https:\/\/arsacs.com\/wp-content\/uploads\/2021\/02\/Anne-McKinney-150x150-2.jpg\")
<\/p>\n
Dr. Anne McKinney, Department of Pharmacology and Therapeutics, McGill University Bellini Life Sciences Bldg
\n3469 Sir William Osler, Montreal, Quebec Canada H3G 0B1
\nTel: (514)-398-5685; Fax: (514)-398-2045; Email: anne.mckinney@mcgill.ca<\/p>\n","protected":false},"excerpt":{"rendered":"
Aim 1 Identifying druggable Targets for potential ARSACS treatment We have recently identified that the endosomal Na+\/H+ exchanger NHE6, which is involved in regulating pH, is downregulated in anterior Purkinje cells of Sacs\uf02d\/\uf02d mice. Interestingly, these are the Purkinje cells that are more susceptible to cell death in ARSACS. Could the loss of NHE6 contribute […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","inline_featured_image":false,"footnotes":""},"categories":[81],"tags":[],"class_list":["post-11988","post","type-post","status-publish","format-standard","hentry","category-recherche-2020"],"yoast_head":"\n