Emerging Roles, Mechanisms, and Therapeutic Potential of Thyroid Hormones in Neurodegenerative Diseases: A Review

Thyroid hormones (THs) are master controllers in the endocrine system and have drawn considerable attention from the research community due to their associations with neurodegenerative diseases as well. In this review article, we present a comprehensive summary of the physiological functions and pathogenic mechanisms of THs in the regulation of several representative neurodegenerative diseases. Our study particularly focuses on Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). AD is the most common cause of dementia, primarily caused by tau protein tangles inside nerve cells and β-amyloid plaques outside, which lead to nerve cell death and brain atrophy. PD is primarily a movement disorder. The degeneration of dopaminergic neurons in the brain impairs the brain's control over muscle activity. MS is usually considered to be an autoimmune demyelinating disease, but it has been found that MS also presents with secondary neurodegenerative pathology, including axonal loss and neuronal damage. In this review, the effects of TH on the pathogeneses of AD, PD, and MS are discussed in detail, with a focus on the following potential mechanisms: neuroprotection, neurogenesis, oxidative stress, and inflammatory response. In addition, we conduct an in-depth review of the possible clinical applications of TH, TH analogs, and thyrotropin-releasing hormone (TRH) in the treatment of AD, PD, and MS based on recent preclinical and clinical studies. By integrating experimental, clinical, and epidemiological results on the effects of TH on neurodegeneration, the present review constructs a theoretical basis for the involvement of TH in the pathogeneses of these diseases in detail. We believe that this basis will be useful for clinical diagnosis and treatment.