在肌萎缩侧索硬化中靶向异常 Nrf2/HO-1 信号：目前对药物靶点的见解和对神经系统疾病的影响

Title:Targeting Abnormal Nrf2/HO-1 Signaling in Amyotrophic Lateral Sclerosis: Current Insights on Drug Targets and Influences on Neurological Disorders

Volume: 21 Issue: 8

关键词: 肌萎缩侧索硬化、nrf2/HO-1、少突胶质细胞、小胶质细胞、星形胶质细胞、神经元细胞、细胞凋亡、运动神经元。

摘要: The nuclear erythroid 2-related-factor (Nrf2) transcription factor/hemoxygenase 1 (HO-1) is a key regulator of an important neuroprotection response by driving the interpretation of various cytoprotective gene to encode for anti-inflammatory, antioxidant, and detoxifying proteins. Various studies investigated that the upregulation of Nrf2/HO-1 has become the potential therapeutic approach in amyotrophic lateral sclerosis (ALS). Amyotrophic lateral sclerosis is a motor neuron disease in which there is a progressive loss of upper motor neuron and lower motor neurons of the motor cortex, brain stem, and corticospinal tract. A result of this upregulation of Nrf2/HO-1 indicates that in the brain, anti-oxidant capacity is reinforced. Further, this shows a cytoprotective effect against oxidative stress in amyotrophic lateral sclerosis. A study reported functions associated with the Nrf2/HO-1 in the neuronal cell, oligodendrocytes, microglia, and astrocytes. Although ALS's pathogenesis is not yet clear, but it is compelling. The evidence shows any dysfunction in the brain such as mitochondrial dysfunction, protein aggregation, glial cell activation, excitotoxicity, and apoptosis which gives ALS-like symptoms. In this review, we have mainly focused on detailing the downregulation of Nrf2/HO-1, which may be the prime reason and may further serve as a pathological hallmark for ALS development. As surveyed, there are limited targetbased interventions that only provide symptomatic relief but do not cure the disease completely. Dysregulation of the Nrf2/HO-1 signaling pathway leads to many physiological changes contributing to neurological conditions, including ALS. Based on the above view, we summarized the combined role of Nrf2/HO-1 signaling in ALS and explored potential therapeutic strategies for disease improvement through pathway modulators.

Cite this article as:

Targeting Abnormal Nrf2/HO-1 Signaling in Amyotrophic Lateral Sclerosis: Current Insights on Drug Targets and Influences on Neurological Disorders, Current Molecular Medicine 2021; 21 (8) . https://dx.doi.org/10.2174/1566524021666210111104920