Malchiodi-Albedi Fiorella, Paradisi Silvia, Matteucci Andrea, Frank Claudio, Diociaiuti Marco
Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Int J Alzheimers Dis. 2011 Feb 8;2011:906964. doi: 10.4061/2011/906964.
Amyloid proteins constitute a chemically heterogeneous group of proteins, which share some biophysical and biological characteristics, the principal of which are the high propensity to acquire an incorrect folding and the tendency to aggregate. A number of diseases are associated with misfolding and aggregation of proteins, although only in some of them-most notably Alzheimer's disease (AD) and transmissible spongiform encephalopathies (TSEs)-a pathogenetic link with misfolded proteins is now widely recognized. Lipid rafts (LRs) have been involved in the pathophysiology of diseases associated with protein misfolding at several levels, including aggregation of misfolded proteins, amyloidogenic processing, and neurotoxicity. Among the pathogenic misfolded proteins, the AD-related protein amyloid β (Aβ) is by far the most studied protein, and a large body of evidence has been gathered on the role played by LRs in Aβ pathogenicity. However, significant amount of data has also been collected for several other amyloid proteins, so that their ability to interact with LRs can be considered an additional, shared feature characterizing the amyloid protein family. In this paper, we will review the evidence on the role of LRs in the neurotoxicity of huntingtin, α-synuclein, prion protein, and calcitonin.
淀粉样蛋白构成了一组化学性质各异的蛋白质，它们具有一些生物物理和生物学特性，其中主要特性是极易发生错误折叠并倾向于聚集。许多疾病都与蛋白质的错误折叠和聚集有关，不过只有其中一些疾病——最显著的是阿尔茨海默病（AD）和传染性海绵状脑病（TSEs）——与错误折叠蛋白质的致病联系如今已得到广泛认可。脂筏（LRs）在多个层面参与了与蛋白质错误折叠相关疾病的病理生理学过程，包括错误折叠蛋白质的聚集、淀粉样生成过程以及神经毒性。在致病性错误折叠蛋白质中，与AD相关的蛋白质淀粉样β（Aβ）是目前研究最多的蛋白质，关于脂筏在Aβ致病性中所起作用，已经积累了大量证据。然而，针对其他几种淀粉样蛋白也收集到了大量数据，因此它们与脂筏相互作用的能力可被视为淀粉样蛋白家族的另一个共同特征。在本文中，我们将综述脂筏在亨廷顿蛋白、α-突触核蛋白、朊病毒蛋白和降钙素神经毒性中作用的相关证据。
