PINK1/Parkin-mediated mitophagy in neurodegenerative diseases

Li, Jie; Yang, Dongming; Li, Zhiping; Zhao, Mengyang; Wang, Dongdong; Sun, Zhixin; Wen, Pei; Dai, Yuexin; Gou, Fengting; Ji, Yilan; Zhao, Deming; Yang, Lifeng

doi:10.1016/j.arr.2022.101817

Cited by 70 publications

(33 citation statements)

References 267 publications

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“…The Parkin RBR E3 Ubiquitin Protein Ligase ( PRKN ) gene encodes a Really Interesting New Gene (RING) domain-containing E3 ubiquitin ligase involved in proteasome-dependent protein degradation. It also plays an important role in mitophagy and autophagy [ 87 ].…”

Section: Resultsmentioning

confidence: 99%

Pediatric-Onset Epilepsy and Developmental Epileptic Encephalopathies Followed by Early-Onset Parkinsonism

Spagnoli

Fusco

Pisani

2023

IJMS

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Genetic early-onset Parkinsonism is unique due to frequent co-occurrence of hyperkinetic movement disorder(s) (MD), or additional neurological of systemic findings, including epilepsy in up to 10–15% of cases. Based on both the classification of Parkinsonism in children proposed by Leuzzi and coworkers and the 2017 ILAE epilepsies classification, we performed a literature review in PubMed. A few discrete presentations can be identified: Parkinsonism as a late manifestation of complex neurodevelopmental disorders, characterized by developmental and epileptic encephalopathies (DE-EE), with multiple, refractory seizure types and severely abnormal EEG characteristics, with or without preceding hyperkinetic MD; Parkinsonism in the context of syndromic conditions with unspecific reduced seizure threshold in infancy and childhood; neurodegenerative conditions with brain iron accumulation, in which childhood DE-EE is followed by neurodegeneration; and finally, monogenic juvenile Parkinsonism, in which a subset of patients with intellectual disability or developmental delay (ID/DD) develop hypokinetic MD between 10 and 30 years of age, following unspecific, usually well-controlled, childhood epilepsy. This emerging group of genetic conditions leading to epilepsy or DE-EE in childhood followed by juvenile Parkinsonism highlights the need for careful long-term follow-up, especially in the context of ID/DD, in order to readily identify individuals at increased risk of later Parkinsonism.

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Section: Resultsmentioning

confidence: 99%

Pediatric-Onset Epilepsy and Developmental Epileptic Encephalopathies Followed by Early-Onset Parkinsonism

Spagnoli

Fusco

Pisani

2023

IJMS

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“…The results indicated that parkin (PARK2) is one of the interaction partners. The main function of parkin is E3 ubiquitin ligase, which is involved in the degradation pathway of specific ubiquitin-labeled proteins to proteasomes or lysosomes [ 25 ]. Additionally, when the mitochondria of cells are abnormal, parkin can recognize the specific protein PINK1 on the outer membrane and clear them by promoting mitophagy [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction

Hong

Tsai

et al. 2023

Cells

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Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to establish effective treatments. In this study, we cloned and sequenced a splice variant of the hydroxysteroid-like 11-β dehydrogenase 1 gene (HSD11B1L) and named it HSD11B1L-181. HSD11 B1L-181 was specifically expressed only in GBM cells. Overexpression of this variant can significantly promote the proliferation, migration and invasion of GBM cells. Knockdown of HSD11B1L-181 expression inhibited the oncogenic potential of GBM cells. Furthermore, we identified the direct interaction of parkin with HSD11B1L-181 by screening the GBM cDNA expression library via yeast two-hybrid. Parkin is an RBR E3 ubiquitin ligase whose mutations are associated with tumorigenesis. Small interfering RNA treatment of parkin enhanced the proliferative, migratory and invasive abilities of GBM. Finally, we found that the alkaloid peiminine from the bulbs of Fritillaria thunbergii Miq blocks the interaction between HSD11B1L-181 and parkin, thereby lessening carcinogenesis of GBM. We further confirmed the potential of peiminine to prevent GBM in cellular, ectopic and orthotopic xenograft mouse models. Taken together, these findings not only provide insight into GBM, but also present an opportunity for future GBM treatment.

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“…Raised cerebrospinal fluid and plasma indicants of autophagy and mitophagy, including PINK1 and parkin, are evident in the active phase of relapse remitting multiple sclerosis, with autophagy inhibition enhancing myelination, highlighting that the enhancement, as well as the suppression, of mitophagy are aspects of 'autoimmune' disorders [53]. Dysregulated mitophagy is evident in many classical 'autoimmune' disorders, including rheumatoid arthritis [54], SLE [55], T1DM [56], myasthenia gravis [57] and autoimmune hepatitis [58], as well as in suspected 'autoimmune' conditions, such as endometriosis [59], and neurodegenerative conditions [60]. Notably, alterations in mitochondrial function and mitophagy are not always evident in cells classically associated with these conditions, but in cells relevant to wider intercellular interactions, including immune cell mitochondria, as evident in Treg in myasthenia gravis [57].…”

Section: Mitochondrial Metabolism and 'Autoimmunity'mentioning

confidence: 99%

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

Anderson¹,

Almulla

Reíter

et al. 2023

Cells

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Although previously restricted to a limited number of medical conditions, there is a growing appreciation that ‘autoimmune’ (or immune-mediated) processes are important aspects of a wide array of diverse medical conditions, including cancers, neurodegenerative diseases and psychiatric disorders. All of these classes of medical conditions are associated with alterations in mitochondrial function across an array of diverse cell types. Accumulating data indicate the presence of the mitochondrial melatonergic pathway in possibly all body cells, with important consequences for pathways crucial in driving CD8+ T cell and B-cell ‘autoimmune’-linked processes. Melatonin suppression coupled with the upregulation of oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising the levels of the major histocompatibility complex (MHC)-1, which underpins the chemoattraction of CD8+ T cells and the activation of antibody-producing B-cells. Many factors and processes closely associated with autoimmunity, including gut microbiome/permeability, circadian rhythms, aging, the aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) all interact with the mitochondrial melatonergic pathway. A number of future research directions and novel treatment implications are indicated for this wide collection of poorly conceptualized and treated medical presentations. It is proposed that the etiology of many ‘autoimmune’/‘immune-mediated’ disorders should be conceptualized as significantly determined by mitochondrial dysregulation, with alterations in the mitochondrial melatonergic pathway being an important aspect of these pathoetiologies.

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PINK1/Parkin-mediated mitophagy in neurodegenerative diseases

Cited by 70 publications

References 267 publications

Pediatric-Onset Epilepsy and Developmental Epileptic Encephalopathies Followed by Early-Onset Parkinsonism

Pediatric-Onset Epilepsy and Developmental Epileptic Encephalopathies Followed by Early-Onset Parkinsonism

Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

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