Acetylated tau in Alzheimer's disease: An instigator of synaptic dysfunction underlying memory loss: Increased levels of acetylated tau blocks the postsynaptic signaling required for plasticity and promotes memory deficits associated with tauopathy.
Acetylated tau in Alzheimer's disease: An instigator of synaptic dysfunction underlying memory loss: Increased levels of acetylated tau blocks the postsynaptic signaling required for plasticity and promotes memory deficits associated with tauopathy.
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DOI：
10.1002/bies.201600224
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Gan L
中科院分区：
文献类型：
--
作者：
Tracy TE;Gan L
tau蛋白病的发病机制涉及tau蛋白在大脑中的积累以及伴随认知能力下降的渐进性突触丧失。病理性 tau 蛋白存在于突触中，它会促进突触功能障碍和记忆缺陷。有毒tau蛋白在破坏调节突触强度的分子网络方面的具体作用一直难以捉摸。 tau 毒性和突触可塑性之间的新机制涉及 tau 上两个赖氨酸 K274 和 K281 的乙酰化，这与阿尔茨海默病 (AD) 中的痴呆有关。我们提出，这些赖氨酸上 tau 乙酰化的增加会阻止海马突触长期增强的表达，从而导致 AD 中的记忆受损。乙酰化 tau 蛋白可以通过干扰记忆相关蛋白 KIBRA 的突触后定位，抑制可塑性所需的突触后 AMPA 型谷氨酸受体的活动依赖性募集。减少 tau 乙酰化的策略可能会导致 AD 认知能力下降的有效治疗。 tau蛋白病是一种与年龄相关的神经退行性疾病，包括阿尔茨海默病，其特征是tau蛋白在大脑中积聚和认知能力下降。我们假设 tau 蛋白病中异常乙酰化 tau 蛋白水平的升高会破坏 KIBRA 依赖性调节突触可塑性的机制，从而导致记忆丧失。
Pathogenesis in tauopathies involves the accumulation of tau in the brain and progressive synapse loss accompanied by cognitive decline. Pathological tau is found at synapses, and it promotes synaptic dysfunction and memory deficits. The specific role of toxic tau in disrupting the molecular networks that regulate synaptic strength has been elusive. A novel mechanistic link between tau toxicity and synaptic plasticity involves the acetylation of two lysines on tau, K274 and K281, which are associated with dementia in Alzheimer’s disease (AD). We propose that an increase in tau acetylated on these lysines blocks the expression of long-term potentiation at hippocampal synapses leading to impaired memory in AD. Acetylated tau could inhibit the activity-dependent recruitment of postsynaptic AMPA-type glutamate receptors required for plasticity by interfering with the postsynaptic localization of KIBRA, a memory-associated protein. Strategies that reduce the acetylation of tau may lead to effective treatments for cognitive decline in AD. Taupathies are age-related neurodegenerative diseases, including Alzheimer’s disease, that are characterized by accumulation of tau protein in the brain and cognitive decline. We hypothesize that enhanced levels of abnormally acetylated tau in tauopathy disrupts the KIBRA-dependent mechanisms that regulate plasticity at synapses leading to memory loss.
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影响因子：
4.6
作者：
Elie A;Prezel E;Guérin C;Denarier E;Ramirez-Rios S;Serre L;Andrieux A;Fourest-Lieuvin A;Blanchoin L;Arnal I
通讯作者：
Arnal I
DOI：
10.1007/s12031-011-9589-0
发表时间：
2011-11
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
Dickson DW;Kouri N;Murray ME;Josephs KA
通讯作者：
Josephs KA
影响因子：
3.7
作者：
Aubry, Soline;Shin, William;Shelanski, Michael L.
通讯作者：
Shelanski, Michael L.
微管相关的蛋白2C在肌动蛋白结合蛋白280缺陷型黑色素瘤细胞系中重新组织微管和微丝中的微丝。
影响因子：
7.8
作者：
Cunningham, C C;Leclerc, N;Flanagan, L A;Lu, M;Janmey, P A;Kosik, K S
通讯作者：
Kosik, K S
影响因子：
16.8
作者：
Cohen TJ;Friedmann D;Hwang AW;Marmorstein R;Lee VM
通讯作者：
Lee VM