2012年10月18日 讯 /生物谷BIOON/ --近日，来自波士顿大学医学院的研究者在亨廷顿氏疾病对大脑损伤效应的研究上取得了新的进展，相关研究成果刊登于国际著名杂志Neurology上，这项研究主要揭示了受亨廷顿氏病影响较大的大脑区域，同时为开辟新型的疗法带来了帮助。
亨廷顿病（HD）是一种遗传性的致死性神经性障碍疾病，当个体在40岁左右时常常会被诊断出该疾病，在1993年研究者鉴别出了该疾病的致病基因，但是其导致特定神经元或脑细胞死亡的原因目前尚不清楚。
这项研究中，研究者对来自HD患者的664份大脑样品进行了研究，他们对受到HD影响的超过50个神经元区域进行了研究分析，结合对亨廷顿基因的特异性突变体的遗传学研究，研究者们分析了来自病人的临床神经学信息。基于上述分析，研究者发现了HD影响大脑主要表现在大脑的两个区域上，纹状体，其位于大脑深层，参与运动控制和不自主运动，是受到HD影响最严重的区域；外部周质区主要参与认知功能和思维处理过程，其也受到HD的损伤，但是相比纹状体，损伤较轻。
于此同时研究者在不同的大脑区域细胞死亡过程中发现了特定的遗传突变，比如，某些个体会出现严重的大脑外皮退化等。研究者Myers表示，当仅仅有一种遗传突变引发亨廷顿氏症时，疾病就会以不同方式在不同人群中影响其大脑不同的区域，首先，我们会测定这些变化，希望鉴别出在特殊个体中发生这种病变的原因并且去预防它。
目前研究者开始进行大范围深入研究，来寻找保护HD患者神经元的特定基因或者其它影响因子的方法，研究者希望这些保护性因子可以为未来HD的疗法带来帮助。（生物谷Bioon.com）
编译自：Pathology of Huntington's Disease Identified
doi:10.1212/WNL.0b013e31826e9a5d
PMC:
PMID:
Assessment of cortical and striatal involvement in 523 Huntington disease brains
Tiffany C. Hadzi, MPH, Audrey E. Hendricks, PhD, Jeanne C. Latourelle, DSc, Kathryn L. Lunetta, PhD, L. Adrienne Cupples, PhD, Tammy Gillis, BSc, Jayalakshmi Srinidhi Mysore, BSc, James F. Gusella, PhD, Marcy E. MacDonald, PhD, Richard H. Myers, PhD* and Jean-Paul Vonsattel, MD*
Objective: To evaluate the relationship of striatal involvement in Huntington disease (HD) to involvement in other brain regions, CAG repeat size, onset age, and other factors. Methods: We examined patterns of neuropathologic involvement in 664 HD brains submitted to the Harvard Brain Tissue Resource Center. Brains with concomitant Alzheimer or Parkinson changes (n = 82), more than 20% missing data (n = 46), incomplete sample submission (n = 12), or CAG repeat less than 36 (n = 1) were excluded, leaving 523 cases. Standardized ratings from 0 (absent) to 4 (severe) of gross and microscopic involvement were performed for 50 regions. Cluster analysis reduced the data to 2 main measures of involvement: striatal and cortical. Results: The clusters were correlated with each other (r = 0.42) and with disease duration (striatal: r = 0.35; cortical: r = 0.31). The striatal cluster was correlated with HD repeat size (r = 0.50). The cortical cluster showed a stronger correlation with decreased brain weight (r = −0.52) than the striatal cluster (r = −0.33). The striatal cluster was correlated with younger death age (r = −0.31) and onset age (r = −0.46) while the cortical cluster was not (r = 0.09, r = −0.04, respectively). Conclusions: The 2 brain clusters had different relationships to the HD CAG repeat size, onset age, and brain weight, suggesting that neuropathologic involvement does not proceed in a strictly coupled fashion. The pattern and extent of involvement varies substantially from one brain to the next. These results suggest that regional involvement in HD brain is modified by factors which, if identified, may lend insight into novel routes to therapeutics.
