Deficient Wnt Signaling and Synaptic Vulnerability in Alzheimer's Disease: Emerging Roles for the LRP6 Receptor.
Deficient Wnt Signaling and Synaptic Vulnerability in Alzheimer's Disease: Emerging Roles for the LRP6 Receptor.
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DOI：
10.3389/fnsyn.2018.00038
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发表时间：
2018
影响因子：
3.7
通讯作者：
Salinas PC
中科院分区：
文献类型：
--
作者：
Buechler J;Salinas PC
突触功能障碍和丧失代表阿尔茨海默病（AD）病理生理学中的关键早期事件。虽然广泛的研究已经阐明了淀粉样蛋白-β（Aβ）寡聚体的直接突触毒性作用，但对Aβ如何影响突触的信号通路知之甚少。更好地了解AD突触脆弱性背后的细胞和分子机制是阐明AD易感性决定因素的关键，并将揭示新的治疗途径。通过Wnt共受体LRP 6的经典Wnt信号传导在维持成人大脑中突触连接的结构和功能完整性方面具有关键作用。越来越多的证据表明，Wnt信号传导的缺陷可能有助于AD病理学。特别是，LRP 6缺陷损害突触功能和稳定性，并有助于AAF产生和斑块形成。在这里，我们审查的作用，Wnt信号的突触维持在成年人的大脑和异常的Wnt信号的突触变性在AD的贡献。我们把重点放在新出现的证据暗示LRP 6受体作为AD风险和病理学的重要调节剂。
Synapse dysfunction and loss represent critical early events in the pathophysiology of Alzheimer’s disease (AD). While extensive research has elucidated the direct synaptotoxic effects of Amyloid-β (Aβ) oligomers, less is known about how signaling pathways at the synapse are affected by Aβ. A better understanding of the cellular and molecular mechanisms underlying synaptic vulnerability in AD is key to illuminating the determinants of AD susceptibility and will unveil novel therapeutic avenues. Canonical Wnt signaling through the Wnt co-receptor LRP6 has a critical role in maintaining the structural and functional integrity of synaptic connections in the adult brain. Accumulating evidence suggests that deficient Wnt signaling may contribute to AD pathology. In particular, LRP6 deficiency compromises synaptic function and stability, and contributes to Aß production and plaque formation. Here, we review the role of Wnt signaling for synaptic maintenance in the adult brain and the contribution of aberrant Wnt signaling to synaptic degeneration in AD. We place a focus on emerging evidence implicating the LRP6 receptor as an important modulator of AD risk and pathology.
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影响因子：
16.6
作者：
Ciani L;Marzo A;Boyle K;Stamatakou E;Lopes DM;Anane D;McLeod F;Rosso SB;Gibb A;Salinas PC
通讯作者：
Salinas PC
影响因子：
7.2
作者：
Cruciat, Cristina-Maria;Niehrs, Christof
通讯作者：
Niehrs, Christof
影响因子：
5.3
作者：
Cong, F;Schweizer, L;Varmus, H
通讯作者：
Varmus, H
影响因子：
3.5
作者：
Beaumont, Vahri;Thompson, Sally-Anne;Munoz-Sanjuan, Ignacio
通讯作者：
Munoz-Sanjuan, Ignacio
影响因子：
16.6
作者：
Viana da Silva S;Haberl MG;Zhang P;Bethge P;Lemos C;Gonçalves N;Gorlewicz A;Malezieux M;Gonçalves FQ;Grosjean N;Blanchet C;Frick A;Nägerl UV;Cunha RA;Mulle C
通讯作者：
Mulle C