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.
