If you're seeing this message, it means we're having trouble loading external resources on our website.

Jeżeli jesteś za filtrem sieci web, prosimy, upewnij się, że domeny *.kastatic.org i *.kasandbox.org są odblokowane.

Główna zawartość

Kurs: MCAT > Rozdział 2

Lekcja 1: Biological sciences practice passage questions

Neurodegeneration and genome mutations


Neurodegeneration is the continuous loss of neuronal structure and function, that often results in neuronal death. In the past twenty years, scientists have determined that neurodegeneration is responsible for a number of mental illnesses, particularly Parkinson’s disease and Alzheimer’s disease. Both of these illnesses are characterized by the presence of Lewy bodies, or protein clumps in the brain. Recent studies explore the underlying cause of neurodegeneration in Parkinson’s disease, and the mechanism of the malfunction on a cellular level.
In one such study, a German family with a history of Parkinson’s disease exhibited an abnormal aggregation of a-synuclein, an abundant protein in the brain. Although its exact function is currently unknown, the protein is thought to be involved in spatial learning, working memory, synaptic rearrangement, and dopamine regulation.
Upon PCR analysis, it was discovered that a mutation in the ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene was present in family members with Parkinson’s disease. The isoleucine at position 93 (codon ATC) was changed to a methionine (codon ATG). However, this mutation was absent in healthy family members.
The mutant protein demonstrates a roughly 50% reduction in catalytic activity compared to the wild-type protein (Table 1).
Table 1: The catalytic activity of the wild-type and mutant protein when expressed in E. coli and presented with the substrate. The weight of each protein is also included. (U) = 1 μmol min1
Wild-type UCH-L1 proteinMutant UCH-L1 protein
Catalytic activity4.08 U mg12.41 U mg1
Weight of protein24.8 kDa24.8 kDa
The UCH-L1 gene exhibits an autosomal dominant inheritance trend in the German family. See Figure 2 for a pedigree analysis of the family.
Figure 2: The figure below is the pedigree tree of 7 individuals in the family. Circles represent females, squares represent males, and shaded individuals indicate those with Parkinson’s disease.
Immunohistochemistry of midbrain sections of a patient with Parkinson’s disease showed a-synuclein and UCH-L1-double-positive Lewy bodies in mesencephalon dopaminergic neurons, suggesting physical and/or functional interaction between the two proteins in patients with Parkinson’s disease.
Leroy, E. Boyer, R. Auburger, G. Leube, B. Ulm, G. Mezey, E. et al. (1998). The ubiquitin pathway in Parkinson's disease. Nature, 451-452.
Yasuda T1, Nihira T, Ren YR, Cao XQ, Wada K, Setsuie R. et al. (2009).Effects of UCH-L1 on alpha-synuclein over-expression mouse model of Parkinson's disease. Journal of neurochemistry, 932-944.
Which of the following is true of the UCH-L1 mutation?
Wybierz 1 odpowiedź: