南加州大学（USC）Keck医学院的研究人员发现了一种与帕金森症（PD）相关的蛋白质的结构线索，最终可能会为神经退行性疾病的治疗带来新的希望。
α-突触核蛋白（α-synuclein）普遍存在于健康人的大脑，不过其功能尚不清楚。这种蛋白质已经成为一个很重要的帕金森氏症的研究课题，那是因为它是在帕金森氏症患者体内发现的蛋白质团块的重要组成部分。
与大多数的蛋白质不同，α-突触核蛋白是典型的刚性结构，它可以折叠并改变其结构。研究人员Tobias S. Ulmer博士和Sowmya Bekshe Lokappa博士在Keck医学院附属的Zilkha Neurogenetic研究所确定了两种不同结构的α-突触核蛋白的能量差距，这个差距这比之前预测的要小。
他们的研究结果于6月17日发表于生物化学杂志 ，这项研究首次量化了能量差：1.2 ± 0.4 kcal/mol。
Ulmer是这项研究的首席研究员，也是Zilkha神经发生研究所生物化学与分子生物学系的副教授，他说：“我们正在试图了解蛋白质折叠和错误折叠的机制， 然后，我们才能明白为什么出错了，这对于治疗像帕金森氏症这样的神经退行性疾病是必不可少的。”
Ulmer说：如果蛋白质的折叠出现了错误，他们会修复或者就此降解。然而，对于周围的神经细胞而言，当α-突触核蛋白的错误折叠超过一定程度，它就变得有毒害作用了，他还补充道：了解其折叠，发现是什么原因导致了异常折叠，这对于确定疾病的根本原因是很关键的。
Ulmer测定了改变蛋白质的结构所需要的能量，他认为，事实上这一过程所需的能量并不是想象中的那么多。这项实验进行于2010年，研究人员通过圆二色光谱，荧光光谱和等温滴定量热法分别测定了延长和破碎的α-突触核蛋白螺旋形式的能量。
南加州大学颅面分子生物学中心博士后研究员、文章的另一位作者Lokappa说：“在折叠的α-突触核蛋白结构中或许存在一种连续的相互转换的状态，可能帮助了它的错误折叠。但我们需要对蛋白质折叠和错误折叠的机制做更好地研究，以解释大脑中究竟出现了什么故障。
该研究是Ulmer关于α-突触核蛋白的一系列研究中的第六项。
帕金森氏症是一种神经疾病，至今没有彻底根治的方法，病因也不明。这是一种慢性退行性疾病。根据国家帕金森基金会的数据，该疾病是第二大最常见的神经退行性疾病，仅次于阿尔茨海默氏症。在美国，该病影响着百万人的健康，世界各地的患者共约400万。（生物探索译）
生物探索推荐英文原文：
USC Researchers Find New Clues About Protein Linked To Parkinson's Disease
Researchers at the Keck School of Medicine of the University of Southern California (USC) have uncovered structural clues about the protein linked to Parkinson's disease (PD), which ultimately could lead to finding a cure for the degenerative neurological disorder.
The alpha-synuclein (α-synuclein) protein is commonly found in the healthy human brain even though its function is not clear. The protein has been the subject of substantial Parkinson's research, however, because it is a major component in the protein clumps found in PD cases.
Unlike most proteins, which are typically rigid and occur in one definitive form, the alpha-synuclein protein can fold and change its structure. Researchers Tobias S. Ulmer, Ph.D. and Sowmya Bekshe Lokappa, Ph.D. at the Keck School-affiliated Zilkha Neurogenetic Institute have determined that the energy difference between two particular alpha-synuclein structures is less than previously speculated.
Their study, to be published in the June 17 issue of The Journal of Biological Chemistry, is the first to quantify that energy difference, 1.2±0.4 kcal/mol.
"We're trying to understand the mechanisms of protein folding and misfolding," said Ulmer, the study's principal investigator and an assistant professor in the Department of Biochemistry and Molecular Biology at the Zilkha Neurogenetic Institute. "Then we can say why something is going wrong, which is essential to treating neurodegenerative disorders like Parkinson's."
If proteins misfold, they are repaired or they break down. However, when alpha-synuclein misfolds it aggregates and becomes toxic to surrounding nerve cells, Ulmer said. Understanding its folding and finding what causes aberrant folding is therefore key to determining the root cause of the disorder, he added.
To put the discovery into perspective, Ulmer compared the energy that researchers thought was needed to change the protein's structure to hurricane-force winds and the actual energy required to a light summer breeze. The experiments were conducted in 2010, measuring the energy of elongated and broken helix forms of alpha-synuclein through circular dichroism spectroscopy, fluorescence spectroscopy and isothermal titration calorimetry.
"There may be a continuous interconversion between folded alpha-synuclein structural states that might contribute to its pathological misfolding," said Lokappa, a post-doctoral research associate at the Center for Craniofacial Molecular Biology at USC and the study's co-author. "But we need to have even better insight into the mechanisms of protein folding and misfolding to explain what's going wrong in the brain."
The paper is the sixth in a series of studies that Ulmer has published on alpha-synuclein.
Parkinson's is a neurological disorder that has no cure or determined cause. It is a slow-progressing degenerative disease that most commonly affects motor function. According to the National Parkinson Foundation, the disorder is the second-most common neurodegenerative disease after Alzheimer's, affecting 1 million people in the United States and some 4 million worldwide.
Researchers at the Keck School of Medicine of the University of Southern California (USC) have uncovered structural clues about the protein linked to Parkinson's disease (PD), which ultimately could lead to finding a cure for the degenerative neurological disorder.
The alpha-synuclein (α-synuclein) protein is commonly found in the healthy human brain even though its function is not clear. The protein has been the subject of substantial Parkinson's research, however, because it is a major component in the protein clumps found in PD cases.
Unlike most proteins, which are typically rigid and occur in one definitive form, the alpha-synuclein protein can fold and change its structure. Researchers Tobias S. Ulmer, Ph.D. and Sowmya Bekshe Lokappa, Ph.D. at the Keck School-affiliated Zilkha Neurogenetic Institute have determined that the energy difference between two particular alpha-synuclein structures is less than previously speculated.
Their study, to be published in the June 17 issue of The Journal of Biological Chemistry, is the first to quantify that energy difference, 1.2±0.4 kcal/mol.
"We're trying to understand the mechanisms of protein folding and misfolding," said Ulmer, the study's principal investigator and an assistant professor in the Department of Biochemistry and Molecular Biology at the Zilkha Neurogenetic Institute. "Then we can say why something is going wrong, which is essential to treating neurodegenerative disorders like Parkinson's."
If proteins misfold, they are repaired or they break down. However, when alpha-synuclein misfolds it aggregates and becomes toxic to surrounding nerve cells, Ulmer said. Understanding its folding and finding what causes aberrant folding is therefore key to determining the root cause of the disorder, he added.
To put the discovery into perspective, Ulmer compared the energy that researchers thought was needed to change the protein's structure to hurricane-force winds and the actual energy required to a light summer breeze. The experiments were conducted in 2010, measuring the energy of elongated and broken helix forms of alpha-synuclein through circular dichroism spectroscopy, fluorescence spectroscopy and isothermal titration calorimetry.
"There may be a continuous interconversion between folded alpha-synuclein structural states that might contribute to its pathological misfolding," said Lokappa, a post-doctoral research associate at the Center for Craniofacial Molecular Biology at USC and the study's co-author. "But we need to have even better insight into the mechanisms of protein folding and misfolding to explain what's going wrong in the brain."
The paper is the sixth in a series of studies that Ulmer has published on alpha-synuclein.
Parkinson's is a neurological disorder that has no cure or determined cause. It is a slow-progressing degenerative disease that most commonly affects motor function. According to the National Parkinson Foundation, the disorder is the second-most common neurodegenerative disease after Alzheimer's, affecting 1 million people in the United States and some 4 million worldwide.
