中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (12): 2685-2686.doi: 10.4103/1673-5374.335817

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

14-3-3ζ-脑源性神经营养因子通路对增强记忆和治疗记忆缺陷的作用

  

  • 出版日期:2022-12-15 发布日期:2022-05-05

Implication of 14-3-3ζ-BDNF pathway in long-lasting memory enhancement and the rescue from memory deficits

Mariam Masmudi-Martín#, Irene Navarro-Lobato#, Zafar U. Khan*   

  1. Brain Metastasis Group, National Cancer Research Centre (CNIO), Madrid, Spain (Masmudi-Martín M)
    Donders Institute for Brain Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands (Navarro-Lobato I)
    Laboratory of Neurobiology, CIMES, University of Malaga, Malaga, Spain; Department of Medicine, Faculty of Medicine, University of Malaga, Malaga, Spain; CIBERNED, Institute of Health Carlos III, Madrid, Spain (Khan ZU)
  • Online:2022-12-15 Published:2022-05-05
  • Contact: Zafar U. Khan, PhD, zkhan@uma.es.
  • Supported by:
    This work was supported by grants from the Ministerio de Economía y Competitividad (BFU2013-43458-R) and Junta de Andalucía (P12-CTS-1694, PI-0542-2013 and CTS-586) to ZUK. 

摘要: http://orcid.org/0000-0003-0742-399X (Zafar U. Khan)

Abstract: Intact memory function is critical for carrying out daily life activities, such as managing finances, remembering to take medications, driving in familiar environments, remembering a grandchild’s birthday, and learning to use a new computer. However, memory deficits not only accompany normal aging but are also comorbid with many psychiatric, neurological, and neurodegenerative diseases. Intellectual disability, autism, attention deficit disorder, learning disability, schizophrenia, and depression all have memory deficit components, as do Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and other neurodegenerative diseases (Khan et al., 2014). Therefore, a large proportion of the human population is affected by this brain disorder. In addition, according to the US Census Bureau and Eurostat estimations, the aged population (individuals over the age of 65 years) will double within three decades. Thus, the number of persons with memory deficits is expected to increase drastically, as is the social and economic burden associated with their treatment and care. Cognition-enhancing pharmacological agents are viewed as a strategy for treating memory deficits or slowing the effects of aging on memory function. Some of the most thoroughly studied examples of memory enhancers are partial agonists of the N-methyl-D-aspartic acid receptor, D-cycloserine and D-serine; synthetic ampakines that allow glutamate to exert a prolonged effect on α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptors; and stimulant drugs that inhibit monoamine reuptake, including amphetamines (Adderall), methylphenidate (Ritalin) and modafinil (Provigil); and donepezil (Aricept), which was designed to inhibit the enzyme acetylcholinesterase, which is responsible for degrading acetylcholine. These agents and other memory enhancers that have been studied to date have failed to produce consistent and invariable effects across various types of memory and have shown limited to no effect on memory deficits. Recently, we discovered that the expression of regulator of G protein signaling 14 of 414 amino acids (RGS14414) in the brain not only induced memory enhancement of multiple types of memory but also was sufficient for the rescue of recognition, spatial, and temporal memory, which are kinds of episodic memory that are primarily affected in patients or individuals with memory dysfunctions, in rodent models of aging and Alzheimer’s disease (López-Aranda et al., 2009; Masmudi-Martín et al., 2019; Navarro-Lobato et al., 2021). This RGS14414-mediated memory enhancement was facilitated through an increase in 14-3-3ζ activity (Navarro-Lobato et al., 2021).