The DOI matches its Crossref record; 89 of the 89 references it cites were found in a registry or an index.
Synaptic, Mitochondrial, and Lysosomal Dysfunction in Parkinson’s Disease
Open accessAbstract
The discovery of genetic forms of Parkinson's disease (PD) has highlighted the importance of the autophagy/lysosomal and mitochondrial/oxidative stress pathways in disease pathogenesis. However, recently identified PD-linked genes, including DNAJC6 (auxilin), SYNJ1 (synaptojanin 1), and the PD risk gene SH3GL2 (endophilin A1), have also highlighted disruptions in synaptic vesicle endocytosis (SVE) as a significant contributor to disease pathogenesis. Additionally, the roles of other PD genes such as LRRK2, PRKN, and VPS35 in the regulation of SVE are beginning to emerge. Here we discuss the recent work on the contribution of dysfunctional SVE to midbrain dopaminergic neurons' selective vulnerability and highlight pathways that demonstrate the interplay of synaptic, mitochondrial, and lysosomal dysfunction in the pathogenesis of PD.
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“Synaptic dysfunction contributes to disease pathogenesis in PD (Nguyen et al. 2019) and may be linked to cognitive and motor dysfunction (Bereczki et al. 2017; Moran et al. 2008).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Nguyen et al. 2019
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Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., Schrag, A.-E., & Lang, A. E. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.13 · Cited by 5,415
International Parkinson's Disease Genomics Consortium (IPDGC), Nalls, M. A., Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), Investigator, T. A. J. D., (CHARGE), C. F. H. A. A. R. I. G. E., North American Brain Expression Consortium (NABEC), et al. (2014) · Nature Genetics · doi:10.1038/ng.3043 · Cited by 1,895
The Role of Oxidative Stress in Parkinson's Disease
Dias, V., Junn, E., & Mouradian, M. M. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130230 · Cited by 1,845
A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci
Chang, D., Nalls, M. A., Hallgrímsdóttir, I. B., Hunkapiller, J., van der Brug, M., Cai, F., International Parkinson's Disease Genomics Consortium, 23andMe Research Team, Kerchner, G. A., Ayalon, G., et al. (2017) · Nature Genetics · doi:10.1038/ng.3955 · Cited by 1,112
Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases
Steger, M., Tonelli, F., Ito, G., Davies, P., Trost, M., Vetter, M., Wachter, S., Lorentzen, E., Duddy, G., Wilson, S., et al. (2016) · eLife · doi:10.7554/elife.12813 · Cited by 1,042
Mitochondria–lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis
Wong, Y. C., Ysselstein, D., & Krainc, D. (2018) · Nature · doi:10.1038/nature25486 · Cited by 911
Self-citationDopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease
Burbulla, L. F., Song, P., Mazzulli, J. R., Zampese, E., Wong, Y. C., Jeon, S., Santos, D. P., Blanz, J., Obermaier, C. D., Strojny, C., et al. (2017) · Science · doi:10.1126/science.aam9080 · Cited by 874
Self-citationActivity-driven local ATP synthesis is required for synaptic function
Rangaraju, V., Calloway, N., & Ryan, T. A. (2014) · Cell · doi:10.1016/j.cell.2013.12.042 · Cited by 836
Complexity of dopamine metabolism
Meiser, J., Weindl, D., & Hiller, K. (2013) · Cell Communication and Signaling · doi:10.1186/1478-811x-11-34 · Cited by 726
Pacelli, C., Giguère, N., Bourque, M.-J., Lévesque, M., Slack, R. S., & Trudeau, L. (2015) · Current Biology · doi:10.1016/j.cub.2015.07.050 · Cited by 530
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Vijiaratnam, N., Simuni, T., Bandmann, O., Morris, H. R., & Foltynie, T. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00061-2 · Cited by 447
Genetics and Pathogenesis of Parkinson's Syndrome
Ye, H., Robak, L. A., Yu, M., Cykowski, M. D., & Shulman, J. M. (2022) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-031521-034145 · Cited by 503
Autophagy in Parkinson's Disease
Hou, X., Watzlawik, J. O., Fiesel, F. C., & Springer, W. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.01.037 · Cited by 361
Glucocerebrosidase and its relevance to Parkinson disease
Do, J., McKinney, C. E., Sharma, P., & Sidransky, E. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0336-2 · Cited by 305
Estrogenic control of mitochondrial function
Klinge, C. M. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101435 · Cited by 326
Metadata
- Authors
- Nguyen, M., Wong, Y. C., Ysselstein, D., Severino, A., & Krainc, D.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Krainc, Dimitri
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 42
- Issue
- 2
- Pages
- 140-149
- ISSN
- 0166-2236 (ISSN-L)
- PMC
- PMC6452863
- OpenAlex
- W2903418495
- Cited by
- 323
- References
- 89
- Citations by year
- 2026: 25 · 2025: 38 · 2024: 53 · 2023: 42 · 2022: 45 · 2021: 57 · 2020: 45 · 2019: 18
- FWCI
- 4.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (2T32AG020506-16, K99 NS109252, T32 NS041234, R01 NS076054, R37 NS096241)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Parkinson's disease, synaptic vesicle endocytosis, mitochondrial dysfunction, oxidative stress, DNAJC6, auxilin, SYNJ1, SH3GL2, endophilin A1, LRRK2, Parkin, VPS35, midbrain dopaminergic neurons, selective neuronal vulnerability, risk genes
- MeSH terms
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Animals, Autophagy, Dopamine, Endocytosis, Humans, Lysosomes, Mitochondria, Parkinson Disease, Synaptic Vesicles, Oxidative Stress, Genetic Predisposition to Disease, alpha-Synuclein, Dopaminergic Neurons
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