日本研究人員一項(xiàng)最新研究成果顯示,，向患有阿爾茨海默氏癥的實(shí)驗(yàn)鼠血管中注射一種基因物質(zhì),，成功使得負(fù)責(zé)分解β淀粉樣蛋白的基因在腦內(nèi)發(fā)揮作用，實(shí)驗(yàn)鼠的病癥得到明顯改善,。這使得將來有可能以接種疫苗的形式來預(yù)防這種常見疾病,。
一種名為腦啡肽酶的分解酶發(fā)揮著防止β淀粉樣蛋白蓄積的功能，β淀粉樣蛋白的蓄積被認(rèn)為是導(dǎo)致阿爾茨海默氏癥的原因,。但隨著年齡增長,，一些人負(fù)責(zé)生成腦啡肽酶的基因功能出現(xiàn)衰退，從而導(dǎo)致發(fā)病,。
日本理化學(xué)研究所18日發(fā)表公報(bào)稱,，該所研究人員和長崎大學(xué)研究人員合作，將腦啡肽酶的基因植入一種無病原性病毒,，并將其注射到患病實(shí)驗(yàn)鼠血管中,。結(jié)果顯示，這種基因只在實(shí)驗(yàn)鼠腦內(nèi)產(chǎn)生作用,，幫助形成腦啡肽酶,，在其他器官中并無功用。研究發(fā)現(xiàn),，接受注射的實(shí)驗(yàn)鼠腦內(nèi)β淀粉樣蛋白比其他患病實(shí)驗(yàn)鼠減少約30％,，學(xué)習(xí)和記憶能力也恢復(fù)到與正常實(shí)驗(yàn)鼠相當(dāng)?shù)乃健?/p>
這種基因注射療法較一些腦神經(jīng)疾病的基因療法更簡單易行，甚至將來有可能實(shí)現(xiàn)阿爾茨海默氏癥的“預(yù)防接種”,。相關(guān)論文已經(jīng)刊登在英國《科學(xué)報(bào)告》（Scientific Reports）雜志上,。（生物谷Bioon.com）
doi:10.1038/srep01472
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Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice
Nobuhisa Iwata; Misaki Sekiguchi; Yoshino Hattori; Akane Takahashi; Masashi Asai; Bin Ji; Makoto Higuchi; Matthias Staufenbiel; Shin-ichi Muramatsu; Takaomi C. Saido
Accumulation of amyloid-β peptide (Aβ) in the brain is closely associated with cognitive decline in Alzheimer's disease (AD). Stereotaxic infusion of neprilysin-encoding viral vectors into the hippocampus has been shown to decrease Aβ in AD-model mice, but more efficient and global delivery is necessary to treat the broadly distributed burden in AD. Here we developed an adeno-associated virus (AAV) vector capable of providing neuronal gene expression throughout the brains after peripheral administration. A single intracardiac administration of the vector carrying neprilysin gene in AD-model mice elevated neprilysin activity broadly in the brain, and reduced Aβ oligomers, with concurrent alleviation of abnormal learning and memory function and improvement of amyloid burden. The exogenous neprilysin was localized mainly in endosomes, thereby effectively excluding Aβ oligomers from the brain. AAV vector-mediated gene transfer may provide a therapeutic strategy for neurodegenerative diseases, where global transduction of a therapeutic gene into the brain is necessary.
(責(zé)任編輯：zengchang
