bims-tofagi Biomed News
on Mitophagy
Issue of 2023–11–26
two papers selected by
Michele Frison, University of Cambridge and Aitor Martínez Zarate, Euskal Herriko Unibertsitatea
  1. Identification of mitophagy-associated proteins profile as potential plasma biomarkers of idiopathic Parkinson's disease.
  2. The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer's Disease Mouse Model.
  1. CNS Neurosci Ther. 2023 Nov 21.
    Identification of mitophagy-associated proteins profile as potential plasma biomarkers of idiopathic Parkinson's disease.
    Shuangjie Qian, Haijun He, Xi Xiong, Ruixue Ai, Wenwen Wang, Huimin Zhu, Qianqian Ye, Shuoting Zhou, Hilde Nilsen, Chenglong Xie.
       BACKGROUND: Despite extensive work to identify diagnostic plasma markers for Parkinson's disease (PD), there are still no accepted and validated surrogate biomarkers. Mitophagy-associated proteins (MAPs), including PTEN-induced putative kinase 1 (PINK1), Parkin, phosphoglycerate mutase 5 (PGAM5), BCL2 interacting protein 3 (BNIP3), and phosphorylated-TBK1 (p-TBK1), are, to our best knowledge, not well studied as a panel of biomarkers of neurodegeneration in PD.
    METHODS: The study population comprised 116 age-matched controls (HC), 179 PD patients, alongside and 90 PD syndromes (PDs) divided between two cohorts: (i) the modeling cohort (cohort 1), including 150 PD, 97 HC, and 80 PDs; and (ii) the validated cohort (cohort 2), including 29 PD, 19 HC, and 10 PDs.
    RESULTS: MAPs are elevated in the plasma of PD patients. PINK1, Parkin, and PGAM5 displayed the top three measurable increase trends in amplitude compared to BNIP3 and p-TBK1. Moreover, the area under the curve (AUC) values of PINK1, PGAM5, and Parkin were ranked the top three MAP candidates in diagnosis accuracy for PD from HC, but the MAPs make it hard to differentiate PD from PDs. In addition, there are higher plasma PINK1-Parkin levels and prominent diagnostic accuracy in A-synuclein (+) subjects than in A-synuclein (-) subjects.
    CONCLUSIONS: These results uncover that plasma MAPs (PINK1, Parkin, and PGAM5) may be potentially useful diagnostic biomarkers for PD diagnosis. Studies on larger cohorts would be required to test whether elevated plasma MAP levels are related to PD risk or prognosis.
    Keywords:  MAPs; Parkinson's disease; biomarkers; diagnosis; mitophagy-associated proteins
    DOI:  https://doi.org/10.1111/cns.14532
  2. Int J Mol Sci. 2023 Nov 20. pii: 16542. [Epub ahead of print]24(22):
    The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer's Disease Mouse Model.
    Da-Ye Lee, Kang-Min Lee, Jee-Hyun Um, Young-Yeon Kim, Dong-Hyun Kim, Jeanho Yun.
      Palmatine, a natural alkaloid found in various plants, has been reported to have diverse pharmacological and biological effects, including anti-inflammatory, antioxidant, and cardiovascular effects. However, the role of palmatine in mitophagy, a fundamental process crucial for maintaining mitochondrial function, remains elusive. In this study, we found that palmatine efficiently induces mitophagy in various human cell lines. Palmatine specifically induces mitophagy and subsequently stimulates mitochondrial biogenesis. Palmatine did not interfere with mitochondrial function, similar to CCCP, suggesting that palmatine is not toxic to mitochondria. Importantly, palmatine treatment alleviated mitochondrial dysfunction in PINK1-knockout MEFs. Moreover, the administration of palmatine resulted in significant improvements in cognitive function and restored mitochondrial function in an Alzheimer's disease mouse model. This study identifies palmatine as a novel inducer of selective mitophagy. Our results suggest that palmatine-mediated mitophagy induction could be a potential strategy for Alzheimer's disease treatment and that natural alkaloids are potential sources of mitophagy inducers.
    Keywords:  Alzheimer’s disease; mitochondrial dysfunction; mitophagy; palmatine
    DOI:  https://doi.org/10.3390/ijms242216542
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