Research Questions

How can oxidative stress contribute to alpha-synuclein pathology/toxicity? What oxidative modifications of alpha-synuclein are relevant to the PD pathogenic process?

There is evidence of oxidative damage in brains of PD patients and anti-oxidant therapies have been explored as disease-modifying therapies for PD. Alpha-synuclein aggregation - in the form of Lewy bodies - is the pathological hallmark of PD. If it a link could be determined between these two pathogenic processes, targeting this common pathway may be a viable approach for developing novel disease-modifying therapies.

04 Feb 2010
Responses: 2
How can the adaptive immune system be targeted as a therapeutic approach for PD?

Neuroinflammation is proposed to be a major factor in creating a toxic environment in the PD brain. However, what is the contribution of the adaptive immune system (ie. T cell function) to PD pathogenesis, and how can we target this system for future therapeutic approaches?

 

03 Feb 2010
Responses: 1
Which LRRK2 kinase substrates identified to date are most likely to be true physiological substrates? What limitations/barriers hinder identification of novel substrates?

Mutations in the gene coding for the putative kinase LRRK2 represent some of the most prevalent genetic factors yet linked to Parkinson’s disease, but how these alterations lead to PD-related pathogenesis remains unclear. A prevailing hypothesis centers around the belief that mutations lead to a toxic gain-of-function in kinase activity; thus, identification of substrates of LRRK2 kinase activity is essential to determining the pathogenic mechanism of LRRK2.

25 Jan 2010
Responses: 9
What species of alpha-synuclein should be targeted for development of PD therapies?

Current theory suggests a possible toxic oligomeric or aggregated form of alpha-synuclein as the trigger for subsequent neurodegeneration in PD, but definitive evidence for this is lacking. Proposed therapeutic approaches focus predominately on breaking up aggregates, or attempt to reduce alpha-synuclein protein levels, either by inhibiting production (e.g, via RNA interference) or enhancing protein turnover. Given current understanding of alpha-synuclein, are these the best approaches for targeting alpha-synuclein therapeutically? What studies are needed to clarify the ideal alpha-synuclein target?

08 Jan 2010
Responses: 5
MJFF Asks: What should the next funding program on PD Subtypes look like?

What are the next practical steps for identifying Parkinson’s disease subtypes that can be useful in guiding treatment and therapeutic development?

This question arose from discussion at a recent MJFF Executive Scientific Advisory Board meeting of the outcomes from the Foundation's '2007 PD Subtypes Program'. Read more details here. Members can post all comments and questions by hitting the 'create response' button on this research question. MJFF will summarize and announce the conclusions of this effort after sufficient discussion has taken place.

23 Dec 2009
Responses: 8
What is the future of PD Genetics?

PD Online member Dr. Andrew Singleton (NIH/NIA) poses the following questions to start this discussion about the future of PD genetics:

  • What will be the impact of the $1000 genome on PD genetics and what are the roadblocks to success?
  • Can we presently understand gene and environment interactions? Will new technologies reveal the interface between genetics and the environment?
  • Is there a role for somatic mutation in Parkinson's disease?
  • What are the ethical considerations as we approach a more complete understanding of the genetic and epigenetic architecture of PD?
  • What would you do with a billion dollars earmarked for genetic research?
23 Dec 2009
Responses: 5
Is Parkinson's a prion disease?

What is your view on the evidence for a prion-like pathological process occurring in PD either as a cause or effect of the disease? What specific steps should be taken next to verify or put to rest this idea?

15 Dec 2009
Responses: 1
How do parkin and PINK1 influence mitochondrial function?

Parkin and PINK1 are two genes implicated in autosomal recessive Parkinson's disease. Parkin is an E3 ligase and a component of the ubiquitin-proteasome system involved in protein turnover while the function of PINK1 is still unclear. Biochemical studies have linked the two in a molecular pathway that entail mitochondrial function, yet how parkin and PINK1 interact, and how these two proteins affect mitochondrial function remains a mystery.

08 Dec 2009
Responses: 6
How strong is the association between pesticide exposure and increased risk for Parkinson's disease and how do we translate this association into therapeutic strategies?

Certain pesticides, including paraquat, rotenone and maneb, have been linked to increased risk for PD. How strong is this association and how does it compare to other known risk factors (such as genetic factors)? What is known about the mechanisms linking pesticide exposure to PD pathogenesis and can this knowledge be translated into actual therapeutic strategies?

25 Nov 2009
Responses: 7
MEMBERS' OPEN FORUM: for rapid-fire posting of your questions and comments.

Not sure where to post your ideas? This is the place! Members hit the orange 'create response' button and start typing your questions and comments.

13 Nov 2009
Responses: 16