Pathways to Parkinsonism

@article{Cookson2003PathwaysTP,
  title={Pathways to Parkinsonism},
  author={Mark R. Cookson},
  journal={Neuron},
  year={2003},
  volume={37},
  pages={7-10}
}
A novel gene for Parkinson's disease (PD), DJ-1, has been identified that encodes a multifunctional product with several known protein-protein interactions and effects on gene expression. Here, I outline how it is possible to construct hypotheses that place DJ-1 in different relationships to the other known PD genes, alpha-synuclein and parkin. The identification of multiple genetic causes will provide further impetus to describe the pathway leading to PD. 
Parkinson's disease: from causes to mechanisms.
TLDR
Novel insights into the degenerative process have been provided by the discovery of genes responsible for rare monogenic parkinsonian syndromes, suggesting that the products of several of these genes can interact with environmental toxins and intervene in molecular pathways controlling the functional integrity of mitochondria. Expand
Crystallizing ideas about Parkinson's disease
  • M. Cookson
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2003
TLDR
The report by Wilson et al. (7) of the detailed crystal structure of DJ-1 adds considerably to the understanding of whatDJ-1 is and what it is not, and all three structures show a similar overall folding pattern and demonstrate that DJ- 1 is a dimer, which is confirmed in two of these papers by additional techniques. Expand
Environmental toxins and α-synuclein in Parkinson’s disease
TLDR
Most of environmental toxins share the common mechanism of causing mitochondria dysfunction by inhibiting complex I and promoting α-synuclein aggregation, a key factor in PD, and understanding the mechanism of interactions between α- synuclein and environmental factors could lead to new therapeutic approaches to PD. Expand
Genetic Factors in Parkinson ’ s Disease and Potential Therapeutic Targets
Parkinson’s disease is a neurodegenerative movement disorder caused by a combination of environmental and genetic factors. Recent human genetic studies have identified five genes that are linked toExpand
Genes and parkinsonism
TLDR
The molecular genetics of Parkinson's disease as currently understood is described to help explain the pathways that underlie neurodegeneration. Expand
Genetic Factors in Parkinsons Disease and Potential Therapeutic Targets
TLDR
Results from this fast expanding field of genetic studies linked to Parkinson's disease are summarized and their potential implication in the treatment of Parkinson’s disease is discussed. Expand
Genetic contributions to Parkinson's disease
TLDR
The identification of multiple genes predisposing to Parkinson's disease will assist in determining the cellular pathway/s leading to the neurodegeneration observed in this disease. Expand
The Role of the Parkinson’s Disease associated Protein DJ-1 in the Development of Diet-induced Obesity in Mice
TLDR
Validation experiments showed that high-fat feeding influences post-translational modifications of DJ-1 and that the loss of Dj-1 accelerates the development of diet-induced obesity in mice. Expand
Genetic clues to the pathogenesis of Parkinson's disease
TLDR
Recent years have seen an explosion in the rate of discovery of genetic defects linked to Parkinson's disease, and these breakthroughs have helped transform research by providing tangible clues to the neurobiology of the disorder. Expand
Genetics of Parkinson's disease: What do mutations in DJ‐1 tell us?
TLDR
The presence of DJ-1 mutations in a large cohort of early onset PD patients, but not in later onset sporadic PD patients is demonstrated and the L166P mutation is confirmed that disrupts dimerization ofDJ-1 through destabilization of the protein. Expand
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