自從1817年James Parkinson在他《關(guān)于震顫麻痹分析》(Essay on the Shaking Palsy)一文中首次描述后,醫(yī)生們一直尋找一種理想的帕金森病診斷方法,。在過去的這幾年里,,可在癥狀出現(xiàn)前理想地認(rèn)出疾病的生物標(biāo)志物已經(jīng)取得較大進展。由英國Lancaster大學(xué)主持的研究已分離了一種血液生物標(biāo)志物,,它有可能作為進行性退行性神經(jīng)疾病的一個簡單血液測試,。
帕金森癥病人表現(xiàn)出在神經(jīng)細(xì)胞內(nèi)有路易小體(Lewy bodies)與蛋白聚集,,和這些含磷酸化與聚集的α-突觸核蛋白 (alpha-synuclein,,α-syn),。在血中,其表達(dá)水平也增加(與無帕金森癥人的相比),,暗示了早期大腦損傷,,甚至在癥狀出現(xiàn)前,。
來自蘭卡斯特大學(xué)健康與藥學(xué)學(xué)院生物醫(yī)學(xué)和生命科學(xué)分部的博士David Allsop,是參與這項工作的研究人員,,他說:"帕金森疾病的血液測試將意味著你能在癥狀出現(xiàn)前發(fā)現(xiàn)處于患病危險中的人,這將有助于保護大腦藥物的開發(fā),,使老人的生活質(zhì)量與未來健康更好。"
在2010年9月,,邁克爾·??怂够鹕鲜辛伺两鹕Y的自發(fā)進展性標(biāo)志物(Progression Markers Initiative),,是4千億美元五年研究發(fā)的帕金森癥的生物標(biāo)志物,。它尤其是一個可早期檢測的生物標(biāo)志物,,能有包括排除其他神經(jīng)疾病在內(nèi)的許多優(yōu)勢,。
在癥狀出現(xiàn)前鑒定疾病能幫助醫(yī)生迅速開始治療和追蹤療效,,與監(jiān)控疾病發(fā)展和給病人及其家屬時間與喪失能力的診斷達(dá)成協(xié)議一樣。它也能讓研究人員開發(fā)靶向此標(biāo)志物的治療方法,,鑒定最可能對此反應(yīng)的病人,。在這個生物標(biāo)志物能被用于診斷或追蹤進程前,還需要更多的研究,,但是它已顯示出可能性,。(生物谷bioon.com)
doi:10.1096/fj.10-179192
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Phosphorylated α-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease
Phosphorylated α-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease
Abstract Parkinson's disease (PD) is characterized by the presence of Lewy bodies containing phosphorylated and aggregated α-synuclein (α-syn). α-Syn is present in human body fluids, including blood plasma, and is a potential biomarker for PD. Immunoassays for total and oligomeric forms of both normal and phosphorylated (at Ser-129) α-syn have been used to assay plasma samples from a longitudinal cohort of 32 patients with PD (sampled at mo 0, 1, 2, 3), as well as single plasma samples from a group of 30 healthy control participants. The levels of α-syn in plasma varied greatly between individuals, but were remarkably consistent over time within the same individual with PD. The mean level of phospho-α-syn was found to be higher (P=0.053) in the PD samples than the controls, whereas this was not the case for total α-syn (P=0.244), oligo-α-syn (P=0.221), or oligo-phospho-α-syn (P=0.181). Immunoblots of plasma revealed bands (at 21, 24, and 50-60 kDa) corresponding to phosphorylated α-syn. Thus, phosphorylated α-syn can be detected in blood plasma and shows more promise as a diagnostic marker than the nonphosphorylated protein. Longitudinal studies undertaken over a more extended time period will be required to determine whether α-syn can act as a marker of disease progression.-Foulds, P. G., Mitchell, J. D., Parker, A., Turner, R., Green, G., Diggle, P., Hasegawa, M., Taylor, M., Mann, D., Allsop, D. Phosphorylated α-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease.