Chromatin plasticity and the pathogenesis of Huntington disease.
Chromatin plasticity and the pathogenesis of Huntington disease.
复制标题
染色质可塑性和亨廷顿病的发病机制。
DOI：
10.1073/pnas.1113321108
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发表时间：
2011
影响因子：
11.1
通讯作者：
Gandy,Sam
中科院分区：
文献类型：
--
作者：
Ehrlich,MichelleE;Gandy,Sam
In PNAS, Hu et al.(1) present strong evidence that pancellular expression of an important chromatin plasticity gene may serve as a biomarker for the state of Huntington disease (HD)“activity,” which, in turn, presumably implies the injurious events caused by polyglutamine cytotoxicity and/or the cellular response to that toxicity. Biomarkers of brain disease are especially valuable because the tissue of interest cannot be conveniently subjected to biopsy for histological analysis. The “gold standard” brain disease biomarker effort to date is represented by the National Institute on Aging Alzheimer’s Disease Neuroimaging Initiative (ADNI)(2). The main focus of ADNI is the annual, serial neuropsychological examination and neuroradiological examination of an age-matched cohort of 400 subjects: 100 cognitively intact elderly subjects, 200 subjects with mild cognitive impairment, and 100 subjects with mild Alzheimer’s disease (AD). One of the most important outcomes of ADNI is the recent realization that approximately one-third of cognitively intact elders have cerebral amyloidosis but no detectable cognitive impairment (3). These biomarker data have revolutionized the approach to AD, leading to an emphasis on prevention trials (4).The ideal disease biomarker (5) has been described as possessing as many of the following characteristics as possible.(i) Visible early, before histopathological changes, and should then be of a magnitude that is proportional to disease progression.(ii) Sensitive, but it should also correlate with the severity of damage.(iii) Accessible in the peripheral tissue.(iv) Analytically stable in tissue, so it can be measured from biopsy and autopsy material.(v) Translational; that is, it should bridge across species.(vi) Associated with a known mechanism. Many current biomarkers are identified through statistical analyses of gene expression, but one should be able to understand the pathophysiologic link between the biomarker and the disease.(vii) Able to localize damage. For example, it should pinpoint the particular area of the organ that has been damaged rather than just indicating toxicity in general.
