中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (7): 1392-1393.doi: 10.4103/1673-5374.300982

• 观点:退行性病与再生 • 上一篇    下一篇

与阿尔茨海默病相关的基因影响海马CA3区的缺血性神经变性

  

  • 出版日期:2021-07-15 发布日期:2021-01-07

Genes associated with Alzheimer’s disease affecting ischemic neurodegeneration of the hippocampal CA3 region

Ryszard Pluta*, Marzena Ułamek-Kozioł   

  1. Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw,  Poland
  • Online:2021-07-15 Published:2021-01-07
  • Contact: Ryszard Pluta, MD, PhD, pluta@imdik.pan.pl.
  • Supported by:
    This work was supported by the Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland (to RP).

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摘要： https://orcid.org/0000-0003-0764-1356 
(Ryszard Pluta)

Abstract: Neurodegeneration in the brain after ischemia with reperfusion mimicking the neuropathology of Alzheimer’s disease: Brain ischemia with reperfusion, which is one of the main causes of morbidity and mortality in the world, triggers various neuropathological changes characteristic for Alzheimer’s disease (AD) such as increased blood-brain barrier permeability, excitotoxicity, necrosis, autophagy, mitophagy, apoptosis, neuroinflammation, amyloid plaques, neurofibrillary tangles, cerebral vessel pathology, and brain atrophy that lead to the death of neurons, deteriorating motor, sensory and cognitive functions (Figure 1) (Kato et al., 1988; Wisniewski et al., 1995; Van Groen et al., 2005; Kocki et al., 2015; Ułamek-Kozioł et al., 2016, 2017, 2019). Brain ischemia is recognized as a major contributor to the dysfunction of an aging brain and the development of neurodegenerative diseases, including AD (Pluta, 2019). The explanation of the final mechanisms of post-ischemic neurodegeneration progress and etiology of AD as well as the development of causal treatment for both diseases seems to involve complicated and complex procedures which require endless revision (Kametani and Hasegawa, 2018; Pluta, 2019). This is partly due to the fact that neurodegenerative processes leading to dementia after both ischemia and AD are not well understood yet. Therefore, there is no causal treatment or adequate criterion for early diagnosis of dementia. Recently, an etiological link has been proposed between dementia following ischemia and dementia due to Alzheimer’s disease (Figure 1) (Salminen et al., 2017; Pluta, 2019). Our article presents facts supporting the idea that neuropathological mechanisms after cerebral ischemia contribute to the development of the genotype and phenotype of AD. The main goal is to broaden knowledge about the overall ischemia processes underlying neuronal death and their impact on regeneration and functional recovery during neurodegeneration of the AD type, and what follows, their relationship with neuronal processes involved in the possible development of AD (Figure 1). Therefore, the main challenge of this new research strategy is to identify genomic and proteomic changes that are common for both ischemia and AD and can be cured. In particular, we are looking for evidence linking the expression of genes associated with AD after ischemia with their role in the regulation of AD proteins in the ischemic brain. Furthermore, we try to understand the role of expression of AD genes along with their proteins during the clinical progress and maturation of post-ischemic brain neurodegeneration with the association of the genotype and phenotype of AD. In this perspective, we combine the importance of cerebral ischemia-induced AD genes expression with a presentation of the final relevant ischemic, genetic mechanism of protein placement in the brain and its reference to the progression of AD. These findings are likely to lead to the development of much-needed new causal therapies and early dementia diagnostic methods in both incurable diseases.