Dissection of pathways involved in polyglutamine disease pathogenesis- identification and analyses of modifier genes
Lead Research Organisation:
University of Cambridge
Department Name: Unlisted
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Publications
Berger Z
(2006)
Deleterious and protective properties of an aggregate-prone protein with a polyalanine expansion.
in Human molecular genetics
Berger Z
(2005)
Lithium rescues toxicity of aggregate-prone proteins in Drosophila by perturbing Wnt pathway.
in Human molecular genetics
Berger Z
(2006)
Rapamycin alleviates toxicity of different aggregate-prone proteins.
in Human molecular genetics
Luo S
(2005)
Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity.
in The Journal of cell biology
Menzies FM
(2006)
Protective roles for induction of autophagy in multiple proteinopathies.
in Autophagy
Ravikumar B
(2005)
Dynein mutations impair autophagic clearance of aggregate-prone proteins.
in Nature genetics
Ravikumar B
(2006)
Rapamycin pre-treatment protects against apoptosis.
in Human molecular genetics
Ravikumar B
(2006)
Role of autophagy in the clearance of mutant huntingtin: a step towards therapy?
in Molecular aspects of medicine
Rubinsztein DC
(2006)
The roles of intracellular protein-degradation pathways in neurodegeneration.
in Nature
Sarkar S
(2007)
Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein.
in The Journal of biological chemistry
Sarkar S
(2005)
Lithium induces autophagy by inhibiting inositol monophosphatase.
in The Journal of cell biology
Underwood BR
(2006)
Huntington disease patients and transgenic mice have similar pro-catabolic serum metabolite profiles.
in Brain : a journal of neurology
Vacher C
(2005)
Overexpression of yeast hsp104 reduces polyglutamine aggregation and prolongs survival of a transgenic mouse model of Huntington's disease.
in Human molecular genetics
| Description | MRC Programme Grant |
| Amount | £2,968,260 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2007 |
| End | 12/2011 |
| Description | Testing rapamycin analogues in neurodegenerative diseases |
| Organisation | Pfizer Ltd |
| Department | Wyeth Pharmaceuticals |
| Country | United States |
| Sector | Private |
| PI Contribution | We are testing rapamycin analogogues for therapeutic efficacy in mouse models of different neurodegenrative diseases |
| Collaborator Contribution | Collaboration |
| Impact | Berger, B Ravikumar, FM. Menzies, L Garcia Oroz, BR Underwood, MN Pangalos, I Schmitt, U Wullner, BO Evert, CJ O'Kane, and DC Rubinsztein (2006). Rapamycin alleviates toxicity of different aggregate-prone proteins. Human Molecular Genetics 15:433-442 |
| Title | Methods and Means for Treating Protein Conformational Disorders. |
| Description | Use of autophagy upregulation for treating neurodegenerative diseases |
| IP Reference | US2007155771 |
| Protection | Patent granted |
| Year Protection Granted | 2007 |
| Licensed | No |
| Impact | USA patent |
| Title | Use of autophagy inducing drugs for neurodegenerative diseases |
| Description | Use of autophagy inducing drugs for neurodegenerative diseases |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2009 |
| Development Status | Under active development/distribution |
| Impact | Currently we are providing proof to expand the use of this strategy beyong Huntington disease |
| Description | School visit - Cambridge |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | talk to school class good feedback from students |
| Year(s) Of Engagement Activity | 2006 |
| Description | Talks at international conferences |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | India-EMBO Autophagy Symposium (Bubaneswar 2017), Autophagy as a Common Pathway in Diseases (NIH, Bethesda 2018), Gordon Conference -Autophagy in Stress, Development and Disease (Il Ciocco, 2018), Interact (Munich, 2018), Autophagy and Neuroprotection (Teaching course, Venice 2018), 83rd Harden Conference Autophagy - from Molecules to Disease (Warwick 2018), Gordon conference - Neurobiology of Brain Disorders (Castelldefels, Spain, 2018), Workshop on Autophagy in model organisms (Budapest, 2018), Autophagy in the healthy and diseased brain - Lake Como School of Advanced Studies (2018), 7th International Student Symposium conducted by the International Max Planck Research School in Chemical and Molecular Biology (Dortmund) (2018) |
| Year(s) Of Engagement Activity | 2018 |
| Description | Talks at international conferences |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Keystone Symposium: Autophagy: From Model Systems to Therapeutic Opportunities (Santa Fe 2019), Autophagy, Inflammation & Metabolism Annual Meeting & Symposium (Albuquerque (2019), British Inflammation Research Association meeting on Autophagy (2019), FASEB - The Protein Aggregation Conference (Snowmass, 2019), Gordon Research Conference on Stress Proteins in Growth, Development and Disease (Barga, 2019), Imperial College Alzheimer's Research Network Symposium (London 2019), EMBO Autophagy Workshop 2019 (Crieff, Scotland), European Society of Neurochemistry 2019 (Milan), Basel Life - Aging and drug discovery and AI (Basel, 2019), Inaugural International Symposium of Cell Fate Determination (Shanghai 2019) |
| Year(s) Of Engagement Activity | 2019 |
| Description | Talks for Medical Students societies |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | St Johns College Medical Society Cambridge (2017) Trinity College Medical Society (2019) |
| Year(s) Of Engagement Activity | 2017,2019 |
| Description | Talks for lay audiences/patients |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Addenbrooke's Hospital Huntington's disease patients (2018); Addenbrooke's Hospital Parkinson's disease patients (2018) |
| Year(s) Of Engagement Activity | 2018 |