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

Author(s):

Elizabeth Minj, Rajeshwar Kumar Yadav and Sidharth Mehan*   Pages 1 - 15 ( 15 )

Abstract:


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 antiinflammatory, anti-oxidant, and detoxifying proteins. Various studies investigated that the upregulation of Nrf2/HO-1 has become the potential therapeutic approach in amyotrophic lateral sclerosis (ALS). As 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. As a result of this upregulation of Nrf2/HO-1 indicates that in brain antioxidant 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 compelling, the evidence shows any dysfunction in the brain such as mitochondrial dysfunction, protein aggregation, glial cell activation, excitotoxicity, and apoptosis 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 target-based 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.

Keywords:

Amyotrophic lateral sclerosis, nrf2/HO-1, oligodendrocytes, microglia, astrocytes, neuronal cell, apoptosis, motor neuron

Affiliation:

Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab



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