Genetic Mutations in Parkinson's Disease - LRRK2

 


Genetic Mutations in Parkinson's Disease | 2019 Udall Center Research Symposium, presented by Dr Valina Dawson

Some very nice slides. 18:18 - 3:00 - 3:26
 
19:25 It is disappointing to see therapies targeting NLRP3 inflammasome inhibition are not more advanced, considering the success of MCC950 in mouse models and how broadly effective it could be for neurodegenerative diseases as well as spinal cord injury.

Index
 
3:00 autosomal recessive PD (ARPD) genes & their functions  
3:26 interaction of ARPD genes - 'linked in circuits' - leading to inactivation of Parkin & activation of PARP1 resulting in death of neurons 
4:56 autosomal dominant - point mutations in alpha synuclein which facilitate its misfolding; a- syn can be duplicated or triplicated 
 6:00 VPS 35 - vacuolar sorting protein 
 6:54 LRRK2 - sporadic PD - spontaneous mutations occur at high frequency - 1-7% of PD patients of European origin and 20-40% of PD in Ashkenazi Jews and North African Arabs (why the higher rate of this specific mutation in these populations?) 
 8:33 LRRK2 is expressed in tissues throughout the body and 
 9:02 LRRK2 plays an important role in immune function - inflammatory bowel disease, Crohn's disease, Leprosy  
9:38 LRRK2 'day jobs' - normal function (as opposed to 'dirty deeds' - gain or loss of function mutations)  
12:54 LRRK2 highly expressing in ribosome  
13:47 LRRK2 phosphorylated ribosomal protein S15  
15:41 RNA translation and protein synthesis in PD  
18:18 Pathways of neurodegeneration in Parkinson's - nice slide summarizing PD pathogenesis - mitochondrial dysfunction  
19:10 clinical trials  
19:25 clinical pipeline

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