Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India.
Department of Pharmacy, School of Chemical Sciences & Pharmacy, Central University of Rajasthan, Bandar Sindri, Kishangarh, Ajmer-305817, Rajasthan, India.
Curr Alzheimer Res. 2019;16(13):1216-1229. doi: 10.2174/1567205016666190903102822.
Alzheimer's Disease (AD) is age-related neurodegenerative disorder recognized by a steadily gradual cognitive decline that has devastating personal and socioeconomic implications. Recently, some genetic factors for AD have been identified which attracted wide attention of researchers in different areas of AD biology and possible new therapeutic targets. Alternative forms of triggering receptor expressed on myeloid cells 2 (TREM2) genes are examples of such risk factors, which contribute higher risk for developing AD. Comprehending TREM2 function pledge to provide salient insight into how neuroinflammation contributes to AD pathology. The dearth of microglial TREM2 shepherd to augmented tau pathology is couple with frequent enhancement of activated neuronal stress kinases. The involvement of TREM2 in the regulation of tau-associated innate immune response of the CNS has clearly demonstrated through these findings. However, whether decrease level of TREM2 assists pathology of tau through changed clearance and pathological escalation of tau or through direct contact between microglia and neuron and any alternative possible mechanisms need to examine. This review briefly summarizes distinct functional roles of TREM2 in AD pathology and highlights the TREM2 gene regulation. We have also addressed the impact of TREM2 on β-amyloid plaques and tau pathology in Alzheimer's disease.
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病，其特征是认知能力逐渐下降，对个人和社会经济造成严重影响。最近，一些 AD 的遗传因素已经被确定，这引起了 AD 生物学不同领域研究人员的广泛关注，并为可能的新治疗靶点提供了依据。触发髓样细胞 2 表达的替代形式的受体（TREM2）基因就是此类风险因素的例子，它们会增加 AD 的发病风险。了解 TREM2 的功能有望深入了解神经炎症如何导致 AD 病理学。TREM2 缺乏导致小胶质细胞 tau 病理学的加剧，同时伴随着激活的神经元应激激酶的频繁增强。这些发现清楚地表明，TREM2 参与了中枢神经系统中与 tau 相关的固有免疫反应的调节。然而，TREM2 水平的降低是否通过改变 tau 的清除和病理级联反应，或者通过小胶质细胞和神经元之间的直接接触以及任何其他可能的机制来协助 tau 的病理学，仍需要进一步研究。本文简要总结了 TREM2 在 AD 病理学中的不同功能作用，并强调了 TREM2 基因的调控。我们还讨论了 TREM2 对阿尔茨海默病中β-淀粉样斑块和 tau 病理学的影响。
