Kaushik Medha, Kaushik Pooja, Parvez Suhel
Department of Toxicology, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi 110062, India.
Department of Toxicology, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi 110062, India.
Ageing Res Rev. 2022 Apr;76:101577. doi: 10.1016/j.arr.2022.101577. Epub 2022 Jan 29.
Age-related cognitive decline is the major cause of concern due to its 70% more incidence than dementia cases worldwide. Moreover, aging is also the major risk factor of Alzheimer's disease (AD), associated with progressive memory loss. Approx. 13 million people will have Alzheimer-related memory decline by 2050. Learning and memory is the fundamental process of brain functions. However, the mechanism for the same is still under investigation. Thus, it is critical to understand the process of memory consolidation in the brain and extrapolate its understanding to the memory decline mechanism. Research on learning and memory has identified several molecular signatures such as Protein kinase M zeta (PKMζ), Calcium/calmodulin-dependent protein kinase II (CaMKII), Brain-derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB) and Activity-regulated cytoskeleton-associated protein (Arc) crucial for the maintenance and stabilization of long-term memory in the brain. Interestingly, memory decline in AD has also been linked to the abnormality in expressing these memory-related molecular signatures. Hence, in the present consolidated review, we explored the role of these memory-related molecular signatures in long-term memory consolidation. Additionally, the effect of amyloid-beta toxicity on these molecular signatures is discussed in detail.
与年龄相关的认知衰退是令人担忧的主要原因,因为其发病率比全球痴呆症病例高出70%。此外,衰老也是阿尔茨海默病(AD)的主要风险因素,与进行性记忆丧失有关。到2050年,约1300万人将出现与阿尔茨海默病相关的记忆衰退。学习和记忆是大脑功能的基本过程。然而,其机制仍在研究中。因此,了解大脑中记忆巩固的过程并将其理解推广到记忆衰退机制至关重要。关于学习和记忆的研究已经确定了几种分子标记,如蛋白激酶Mζ(PKMζ)、钙/钙调蛋白依赖性蛋白激酶II(CaMKII)、脑源性神经营养因子(BDNF)、环磷酸腺苷反应元件结合蛋白(CREB)和活性调节细胞骨架相关蛋白(Arc),它们对大脑中长期记忆的维持和稳定至关重要。有趣的是,AD中的记忆衰退也与这些与记忆相关的分子标记表达异常有关。因此,在本综述中,我们探讨了这些与记忆相关的分子标记在长期记忆巩固中的作用。此外,还详细讨论了淀粉样β毒性对这些分子标记的影响。