Grant: Operating Grant - Priority Announcement: Neuromuscular Research
University of British Columbia
$89,576.00
Misfolding of Cu/Zn superoxide dismutase by pathological FUS and TDP43: relevance to amyotrophic lateral sclerosis
FY 2011-12
Summary
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is an incurable neuromuscular disease characterized by progressive paralysis of the muscles of the limbs, speech, swallowing, and respiration due to the progressive degeneration of motor neurons. Multiple laboratories, including our own, have recently shown that protein misfolding of Cu/Zn superoxide dismutase (SOD1) can be propagated in cell culture in a prion-like manner. However, genetic mutations of FUS and TDP43, in addition to SOD1 and some others can all result in clinicopathologically indistinguishable ALS. In this research, we test the hypothesis that misfolded and/or mislocalized FUS and TDP43 can trigger the misfolding of SOD1, which is subsequently propagated throughout the motor nervous system in ALS. Understanding the final common molecular pathway of ALS will aid in the identification of novel diagnostics and treatment targets for this devastating disease.
Department
Program
Operating Grant - Priority Announcement: Neuromuscular Research
Recipient
Location
British Columbia, Canada
Recipient Type
Academia
Type
Grant
Source
CIHR Funding Decisions Database
As published
Id
259206
Name
Cashman Neil R
Region
British Columbia
Country
Canada
Orgtype
Institution Paid; Research Institution
Partnername
Amyotrophic Lateral Sclerosis Society of Canada
Instname2
Neurosciences, Mental Health and Addiction
Theme2
Biomedical
Prcname2
Systems & Circuits Neurosciences - A
Projecttitle
Misfolding of Cu/Zn superoxide dismutase by pathological FUS and TDP43: relevance to amyotrophic lateral sclerosis
Programtype2
Operating Grants
Orgnameinp2
University of British Columbia
Cihramount2
$89,576
Cihrequipment2
$0
Programname2
Operating Grant - Priority Announcement: Neuromuscular Research
Keyworddelim
Amyotrophic Lateral Sclerosis; Neurodegeneration; Prion-Like; Protein Misfolding; Rna Processing; Template Directed Misfolding
Abstract
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is an incurable neuromuscular disease characterized by progressive paralysis of the muscles of the limbs, speech, swallowing, and respiration due to the progressive degeneration of motor neurons. Multiple laboratories, including our own, have recently shown that protein misfolding of Cu/Zn superoxide dismutase (SOD1) can be propagated in cell culture in a prion-like manner. However, genetic mutations of FUS and TDP43, in addition to SOD1 and some others can all result in clinicopathologically indistinguishable ALS. In this research, we test the hypothesis that misfolded and/or mislocalized FUS and TDP43 can trigger the misfolding of SOD1, which is subsequently propagated throughout the motor nervous system in ALS. Understanding the final common molecular pathway of ALS will aid in the identification of novel diagnostics and treatment targets for this devastating disease.
Competitiondate
201203
Approvedterm2
3 yrs 0 mth
Pinamesdelim
Cashman, Neil R
Approvedterm
3 ans 0 mois
Cihrcontribution2
Inst of Neurosc Mental Hlth &A~ $89,576~ $0~
