Regional Neurogenetic Center (CRN), Department of Primary Care, ASP Catanzaro, 88046 Lamezia Terme, Italy.
Laboratory of Ancient DNA, Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, Italy.
Int J Mol Sci. 2023 Feb 6;24(4):3200. doi: 10.3390/ijms24043200.
Alzheimer's disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space () and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; ). The Nerve growth factor receptor (NGFR/p75) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., proNGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75 making it the "ideal" candidate in mediating Aβ-induced neuropathology. In addition to pathogenesis and neuropathology, several data indicated that NGFR/p75 could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75 could represent a good diagnostic tool, as well as a promising therapeutic target for AD. Here, we comprehensively summarize and review the current experimental evidence on this topic.
阿尔茨海默病（AD）是老年人最常见的痴呆类型，主要特征是大脑中β淀粉样蛋白（Aβ）肽的积累，这些肽来自淀粉样前体蛋白（APP），在细胞外空间（）和蛋白质 tau 的过度磷酸化形式的细胞内沉积物（p-tau；）。神经生长因子受体（NGFR/p75）是所有已知哺乳动物神经营养因子（即 proNGF、NGF、BDNF、NT-3 和 NT-4/5）的低亲和力受体，它参与决定神经元存活和死亡的途径。有趣的是，Aβ肽也可以使 NGFR/p75失明，使其成为介导 Aβ诱导的神经病理学的“理想”候选物。除了发病机制和神经病理学，一些数据表明，NGFR/p75 也可以从遗传角度在 AD 中发挥关键作用。其他研究表明，NGFR/p75 可能是一种很好的诊断工具，也是治疗 AD 的有希望的靶点。在这里，我们全面总结和回顾了这一主题的当前实验证据。
