Dataset Information

Targeting PINK1 Using Natural Products for the Treatment of Human Diseases.

ABSTRACT: PINK1, also known as PARK6, is a PTEN-induced putative kinase 1 that is encoded by nuclear genes. PINK1 is ubiquitously expressed and regulates mitochondrial function and mitophagy in a range of cell types. The dysregulation of PINK1 is associated with the pathogenesis and development of mitochondrial-associated disorders. Many natural products could regulate PINK1 to relieve PINK1-associated diseases. Here, we review the structure and function of PINK1, its relationship to human diseases, and the regulation of natural products to PINK1. We further highlight that the discovery of natural PINK1 regulators represents an attractive strategy for the treatment of PINK1-related diseases, including liver and heart diseases, cancer, and Parkinson's disease. Moreover, investigating PINK1 regulation of natural products can enhance the in-depth comprehension of the mechanism of action of natural products.

SUBMITTER: Li YQ

PROVIDER: S-EPMC8572127 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Targeting PINK1 Using Natural Products for the Treatment of Human Diseases.

Li Yan-Qin YQ Zhang Fan F Yu Li-Ping LP Mu Jian-Kang JK Yang Ya-Qin YQ Yu Jie J Yang Xing-Xin XX

BioMed research international 20211030

PINK1, also known as PARK6, is a PTEN-induced putative kinase 1 that is encoded by nuclear genes. PINK1 is ubiquitously expressed and regulates mitochondrial function and mitophagy in a range of cell types. The dysregulation of PINK1 is associated with the pathogenesis and development of mitochondrial-associated disorders. Many natural products could regulate PINK1 to relieve PINK1-associated diseases. Here, we review the structure and function of PINK1, its relationship to ...[more]

PMID: 34751247

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Project description:Misfolded proteins are the main common feature of neurodegenerative diseases, thereby, normal proteostasis is an important mechanism to regulate the neural survival and the central nervous system functionality. The ubiquitin-proteasome system (UPS) is a non-lysosomal proteolytic pathway involved in numerous normal functions of the nervous system, modulation of neurotransmitter release, synaptic plasticity, and recycling of membrane receptors or degradation of damaged and regulatory intracellular proteins. Aberrant accumulation of intracellular ubiquitin-positive inclusions has been implicated to a variety of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease (HD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Myeloma (MM). Genetic mutation in deubiquitinating enzyme could disrupt UPS and results in destructive effects on neuron survival. To date, various agents were characterized with proteasome-inhibitory potential. Proteins of the ubiquitin-proteasome system, and in particular, E3 ubiquitin ligases, may be promising molecular targets for neurodegenerative drug discovery. Phytochemicals, specifically polyphenols (PPs), were reported to act as proteasome-inhibitors or may modulate the proteasome activity. PPs modify the UPS by means of accumulation of ubiquitinated proteins, suppression of neuronal apoptosis, reduction of neurotoxicity, and improvement of synaptic plasticity and transmission. This is the first comprehensive review on the effect of PPs on UPS. Here, we review the recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders. This review attempts to summarize the latest reports on the neuroprotective properties involved in the proper functioning of natural polyphenolic compounds with implication for targeting ubiquitin-proteasome pathway in the neurodegenerative diseases. We highlight the evidence suggesting that polyphenolic compounds have a dose and disorder dependent effects in improving neurological dysfunctions, and so their mechanism of action could stimulate the UPS, induce the protein degradation or inhibit UPS and reduce protein degradation. Future studies should focus on molecular mechanisms by which PPs can interfere this complex regulatory system at specific stages of the disease development and progression.

Dataset Information

Targeting PINK1 Using Natural Products for the Treatment of Human Diseases.

Publications

Targeting PINK1 Using Natural Products for the Treatment of Human Diseases.

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