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Cited by 482Parkinson's Disease Mechanisms and TreatmentsAutophagy in Disease and TherapyNuclear Receptors and Signaling

Mitochondrial dysfunction and mitophagy in parkinson’s disease: from mechanism to therapy

Malpartida, Ana Belen, Williamson, Matthew, Narendra, Derek P., Wade-Martins, Richard, Ryan, Brent J.·2021·Trends in Biochemical Sciences
DOI 10.1016/j.tibs.2020.11.007
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Abstract

Mitochondrial dysfunction has been associated with neurodegeneration in Parkinson's disease (PD) for over 30 years. Despite this, the role of mitochondrial dysfunction as an initiator, propagator, or bystander remains undetermined. The discovery of the role of the PD familial genes PTEN-induced putative kinase 1 (PINK1) and parkin (PRKN) in mediating mitochondrial degradation (mitophagy) reaffirmed the importance of this process in PD aetiology. Recently, progress has been made in understanding the upstream and downstream regulators of canonical PINK1/parkin-mediated mitophagy, alongside noncanonical PINK1/parkin mitophagy, in response to mitochondrial damage. Progress has also been made in understanding the role of PD-associated genes, such as SNCA, LRRK2, and CHCHD2, in mitochondrial dysfunction and their overlap with sporadic PD (sPD), opening opportunities for therapeutically targeting mitochondria in PD.

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  • Infants with Krabbe disease develop alpha-synuclein inclusions that exhibit prion-like spread similar to the alpha-synuclein of PD.

    “In addition to accumulating glycosphingolipids, infants with Krabbe disease develop alpha-synuclein inclusions that exhibit prion-like spread similar to the alpha-synuclein of PD.104”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [104]

    The α-synuclein section discusses aggregation and Lewy bodies in Parkinson’s disease, but does not address infants with Krabbe disease or prion-like spread. Searches for Krabbe disease, glycosphingolipids, and prion-like spread found no passage supporting the attributed claim. (LLM, conf=0.72)

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Sorted by citations

Authors
Malpartida, A. B., Williamson, M., Narendra, D. P., Wade-Martins, R., & Ryan, B. J.
Affiliations
  • University of Oxford (GB)
  • National Institute of Neurological Disorders and Stroke (US)
Corresponding author
Ryan, Brent J.
ORCID
Venue
Trends in Biochemical Sciences
Publisher
Elsevier BV
Published
2021-04
Volume
46
Issue
4
Pages
329-343
ISSN
0968-0004 (ISSN-L)
DOI
10.1016/j.tibs.2020.11.007
OpenAlex
W3111927179
Cited by
482
References
8
Citations by year
2026: 71 · 2025: 97 · 2024: 94 · 2023: 94 · 2022: 88 · 2021: 38
FWCI
6.17
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Trends in Biochemical Sciences (publishedVersion)
  • PubMed (publishedVersion)
Funders
Monument Trust Discovery Award (J-1403)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, mitochondrial dysfunction, mitophagy, PINK1, Parkin, SNCA, LRRK2, CHCHD2, sporadic Parkinson's disease, neurodegeneration, mitochondrial damage
MeSH terms
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, PTEN-Induced Putative Kinase, DNA-Binding Proteins, Humans, Mitochondria, Parkinson Disease, Protein Kinases, Transcription Factors, Ubiquitin-Protein Ligases, alpha-Synuclein, Mitophagy

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