Parkinson’s Disease genetics

Forloni, G., Terreni, L., Bertani, I., et al. (2002) Protein misfolding in Alzheimer s and Parkinson s disease genetics and molecular mechanisms. NeurobioL Aging, 23, 957-976. 

Abbas, N., Lucking, C. B., Ricard, S., Durr, A., Bonifati, V., et al. 1999. A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson s Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson s Disease. Hum Mol Genet 8 567-74. 

Parkinson s disease proteolytic stress, which recently has been characterized in connection with rare Parkinson s disease genetic mutations as well as environmental and/or endogenous neurotoxicants, mitochondrial dysfunction, and oxidative metabolism—any and all of which may lead to oxidative stress. This section describes these and some alternative proposals regarding the etiology of Parkinson s disease. 

Steece-CoUier, K., E. Maries, and J. H. Kordower. Etiology of Parkinson s disease Genetics and environment revisited, 99(22), 2002 13972-4. 

Parkinson s disease 253-4, 298 pathophysiology of iron in humans 228 absorption disorders 211-20 acquired and genetic disorders 207 deficiency... 

Riess, O., Berg, D., Kruger, R. and Schulz, J. B. Therapeutic strategies for Parkinson s disease based on data derived from genetic research. /. Neurol. 250 13-10,2003. 

Farrer, M., Maraganore, D. M., Lockhart, P. etal. alpha-Synuclein gene haplotypes are associated with Parkinson s disease. Hum. Mol. Genet. 10 1847-1851,2001. 

Lewy body filaments are made of a-synuclein. Shortly after the identification of the genetic defect responsible for Parkinson s disease in the Contursi kindred, Lewy bodies and Lewy neurites in the substantia nigra from patients with sporadic Parkinson s disease were shown to be strongly immunoreactive for a-synuclein [7] (Fig. 45-3). Subsequently, Lewy body filaments were found to be... 

The cause of Alzheimer s disease is unknown, but genetic factors clearly play a role. One clue supporting this view is provided by the observation that individuals with Down syndrome, a common cause of mental retardation, frequently develop a dementia similar to Alzheimer s disease during early adulthood. Vascular dementia, which is also called multi-infarct dementia, results from the accumulation of tiny strokes. Individually, these strokes or infarcts are too small to cause any noticeable problem, but as they accumulate, they produce deficits similar to Alzheimer s disease. Other neurological diseases such as Parkinson s disease, Pick s disease, and Huntington s disease cause slow deterioration of the brain that ultimately leads to a degenerative dementia. 

It should be noted that the genetic information for the P450 enzymes is present throughout in all tissues, but knowledge of the role of the enzymes in tissues other than the liver and gastrointestinal tract is unclear. For example, cytochrome P450 2D6 is found in the brain where it is linked to the dopamine transporter. Whether a deficit in the activity of this enzyme is responsible for predisposing some individuals to Parkinson s disease is a matter of conjecture. 

Fairer, M., Gwinn-Hardy, K., Muenter, M., DeVrieze, F. W., Crook, R., et al. 1999. A chromosome 4p haplotype segregating with Parkinson s disease and postural tremor. Hum Mol Genet 8 81—5. 

Gasser, T., Muller-Myhsok, B., Wszolek, Z. K., Oehlmann, R., Caine, D. B., et al. 1998. A susceptibility locus for Parkinson s disease maps to chromosome 2pl3. Nat Genet 18 262—5. 

Gasser T Update on the genetics of Parkinson s disease. Mov Disord 2007 22(Suppl 17) S343. 

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