Research Questions
Find here a short-list of PD papers added to Pubmed in the last week. Has one caught your eye? Is your favorite paper not on the list? Should one of these not have made the cut? Add your comments below by logging in and posting a response.
08 Mar 2010
Responses: 12
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.
04 Mar 2010
Responses: 8
An important step in moving novel neuroprotective agents towards the clinic involves testing the efficacy of therapeutics in preclinical models. Many different preclinical models are available for PD research and decisions about their specific use depends on the particular therapeutic/mechanism under investigation. However, some general issues arise when designing these preclinical tests and controversy exists as to the best outcome measures that should be employed.
24 Feb 2010
Responses: 15
As is the case in other diseases, the current gold standard methodology
for testing the efficacy of experimental Parkinson’s disease
therapeutics involves the placebo-controlled study design. However,
positive placebo responses have been reported in a number of PD trials,
complicating the interpretation of efficacy results. These findings
make interpretation of potential efficacy of an experimental treatment
in an open-labeled study design extremely difficult and also raise the
barriers for the design and interpretation of placebo-controlled trials
in PD. Furthermore, as is the case with other diseases, the underlying
basis for the placebo response in PD patients is poorly understood.
19 Feb 2010
Responses: 10
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. Furthermore, whether (and how) LRRK2 might relate to other PD-related factors has yet to be determined. The observation of varied alpha-synuclein and tau-related pathology in some post-mortem tissue from people with LRRK2-linked PD suggests a complex mechanistic picture.
12 Feb 2010
Responses: 4
Mitochondrial
dysfunction has been found in brain and other body tissue in
Parkinson's disease patients. Additionally, many environmental agents
implicated in PD, such as pesticides, function as mitochondrial
inhibitors. The exact role for mitochondrial function in the etiology
of PD remains controversial.
11 Feb 2010
Responses: 7
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
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
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
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