Mitochondrial UCP1: Potential thermogenic mechanistic switch for the treatment of obesity and neurodegenerative diseases using natural and epigenetic drug candidates

• Published in: Phytomedicine (Stuttgart) Vol. 130; p. 155672
• Main Authors: Reyad-ul-Ferdous, Md, Gul, Ijaz, Raheem, Muhammad Akmal, Pandey, Vijay, Qin, Peiwu
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 25.07.2024
• Subjects: adipocytes; Adipose tissue; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Alzheimer disease; Alzheimer's disease and Parkinson's disease; Animals; biogenesis; Biological Products - pharmacology; brown adipose tissue; calcium; drugs; Epigenesis, Genetic - drug effects; epigenetics; free fatty acids; free radicals; heat production; Humans; Mitochondria; Mitochondria - drug effects; Neurodegenerative Diseases - drug therapy; neurons; neuroplasticity; neuroprotective effect; Obesity; Obesity - drug therapy; Parkinson disease; synaptic transmission; temperature; therapeutics; Thermogenesis; Thermogenesis - drug effects; toxicity; UCPs; Uncoupling Protein 1 - genetics; Uncoupling Protein 1 - metabolism; FFA; Adipose tissue; ATGL; HFD; UCP1; CNS; WAT; COVID-19; Mitochondria; pufas; TRP; PPAR; UCPs; CAGR; BMI; WHO; HSL; Obesity; lcfas; GLP-1; TRPV; ISO; IMM; DIO2; tags; SIRT-1; MAG; Thermogenesis; TH; BAT; ETC; AMPK; Alzheimer's disease and Parkinson's disease; FA; MPTP; DHA; PL; lxrs; TZD
• ISSN: 0944-7113; 1618-095X; 1618-095X
• DOI: 10.1016/j.phymed.2024.155672

Brown fat is known to provide non-shivering thermogenesis through mitochondrial uncoupling mediated by uncoupling protein 1 (UCP1). Non-shivering is not dependent on UCP2, UCP4, and BMCP1/UCP5 genes, which are distinct from UCP1 in a way that they are not constitutive uncouplers. Although they are susceptible to free fatty acid and free radical activation, their functioning has a significant impact on the performance of neurons. Using subject-specific keywords (Adipose tissue; Adipocytes; Mitochondria; Obesity; Thermogenesis; UCP's in Neurodegeneration; Alzheimer's disease; Parkinson's disease), research articles and reviews were retrieved from Web of Science, ScienceDirect, Google Scholar, and PubMed. This article includespublications published between 2018 and 2023. The drugs that upregulate UCP1 are included in the study while the drugs that do not impact UCP1 are were not included. Neuronal UCPs have a direct impact on synaptic plasticity, neurodegenerative processes, and neurotransmission, by modulating calcium flux, mitochondrial biogenesis, local temperature, and free radical generation. Numerous significant advances in the study of neuronal UCPs and neuroprotection are still to be made. Identification of the tissue-dependent effects of UCPs is essential first. Pharmacologically targeting neuronal UCPs is a key strategy for preventing both neurodegenerative diseases and physiological aging. Given that UCP2 has activities that are tissue-specific, it will be essential to develop treatments without harmful side effects. The triggering of UCPs by CoQ, an essential cofactor, produces nigral mitochondrial uncoupling, reduces MPTP-induced toxicity, and may even decrease the course of Parkinson's disease, according to early indications. Herein, we explore the potential of UCP1 as a therapeutic target for treating obesity, neurodegenerative diseases as well as a potential activator of both synthetic and natural drugs. A deeper knowledge of synaptic signaling and neurodegeneration may pave the way to new discoveries regarding the functioning and controlling of these genes.