(Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis.
(Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis.
复制标题
β-淀粉样蛋白对突触活动和神经递质释放的调节：阿尔茨海默病发病机制之外的展望。
DOI：
10.3389/fnmol.2021.635880
复制
发表时间：
2021
影响因子：
4.8
通讯作者：
Govoni S
中科院分区：
文献类型：
--
作者：
Fagiani F;Lanni C;Racchi M;Govoni S
β-淀粉样蛋白（Aβ）是神经元代谢的一种可溶性产物，在阿尔茨海默病（AD）的发病机制中发挥重要作用，对突触可塑性、记忆和神经递质的释放具有神经调节作用。已观察到这种效应以激素方式发生，Aβ表现出双重作用，受其浓度、不同亚型或肽聚集形式的影响。然而，迄今为止，我们对Aβ的生理功能，特别是其在正常大脑中对突触活动和神经传递的调节作用的了解是零碎的，从而阻碍了对从功能紊乱到功能障碍的生物学机制的清晰理解。特别是，根据淀粉样蛋白级联假说，从生理学到病理学的转变与Aβ水平的异常增加有关，这是由于Aβ产生和清除的不平衡。在这方面，已经假设增加的Aβ水平诱导突触功能的早期缺陷，并且已经建议这种改变至少部分地解释神经精神症状的发作（例如，冷漠、焦虑、情绪变化、抑郁和激越/攻击性），经常在AD的前驱期观察到。因此，了解AD早期突触改变的生物学机制是确定AD治疗相关时间窗和深入了解AD发病机制的关键起点。
Beside its widely studied role in the pathogenesis of Alzheimer's disease (AD), β-amyloid (Aβ) is a normal and soluble product of neuronal metabolism that regulates several key physiological functions, exerting neuromodulatory effects on synaptic plasticity, memory, and neurotransmitter release. Such effects have been observed to occur in a hormetic fashion, with Aβ exhibiting a dual role influenced by its concentration, the different isoforms, or aggregation forms of the peptide. However, to date, our knowledge about the physiological functions of Aβ and, in particular, its modulatory role on synaptic activity and neurotransmission in the normal brain is fragmentary, thus hindering a clear comprehension of the biological mechanisms underlying the derangement from function to dysfunction. In particular, according to the amyloid cascade hypothesis, the switch from physiology to pathology is linked to the abnormal increase in Aβ levels, due to an imbalance in Aβ production and clearance. In this regard, increased Aβ levels have been hypothesized to induce early defects in synaptic function and such alterations have been suggested to account, at least in part, for the onset of neuropsychiatric symptoms (e.g., apathy, anxiety, changes in mood, depression, and agitation/aggression), frequently observed in the prodromal stage of AD. Therefore, understanding the biological mechanisms underlying early synaptic alterations in AD is a key starting point to frame the relevant time windows for AD treatment and to gain insight into AD etiopathogenesis.
登录
查看更多内容
DOI：
10.1126/science.1180962
发表时间：
2009-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kang JE;Lim MM;Bateman RJ;Lee JJ;Smyth LP;Cirrito JR;Fujiki N;Nishino S;Holtzman DM
通讯作者：
Holtzman DM
影响因子：
4.8
作者：
Lazarevic V;Fieńko S;Andres-Alonso M;Anni D;Ivanova D;Montenegro-Venegas C;Gundelfinger ED;Cousin MA;Fejtova A
通讯作者：
Fejtova A
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
16.2
作者：
Kamenetz, F;Tomita, T;Malinow, R
通讯作者：
Malinow, R
影响因子：
17.1
作者：
Iliff JJ;Wang M;Liao Y;Plogg BA;Peng W;Gundersen GA;Benveniste H;Vates GE;Deane R;Goldman SA;Nagelhus EA;Nedergaard M
通讯作者：
Nedergaard M