Striatal glutamatergic hyperactivity in Parkinson's disease
Open accessAbstract
Glutamatergic hyperactivity in the nucleus striatum, the main basal ganglia input, has been involved in the progression of Parkinson's disease (PD) and the onset of L-Dopa-induced dyskinesias (LIDs). Abnormalities in the spiny projection neurons excitability and firing, and in the overactivity of glutamate transmission found in animal models of PD, pointed to the synaptic dysfunctions as a primary target to counteract alterations before overt neurodegeneration, conferring a key role to striatal glutamatergic transmission in the early phases of the disease. The present paper provides an overview of the evidence that glutamatergic overactivity is a critical mechanism underlying different PD-associated striatal alterations in early and advanced symptomatic stages of the disease. These aberrant changes, under L-Dopa therapy, lead to a more complex synaptopathy that involves other neurotransmitter systems and persistent modifications to generate LIDs. The review discusses the main changes in glutamatergic functions found in PD preclinical models and clinical studies and an update of the current pharmacological strategies to modulate the glutamatergic systems at the pre- and postsynaptic levels will be provided.
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Aberrant glutamatergic neurotransmission is a key contributing factor to neurodegeneration and Parkinson's disease.
“Aberrant glutamatergic neurotransmission represents a key contributing factor to neurodegeneration and PD.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [539]
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Flagged first, then by citations
Research works printed but not linked: 1
- Kandel, E.R., et al., 2003. In: Ambrosiana (Ed.), Principi di neuroscienze.
Cited by
Sorted by citations
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
- Authors
- Campanelli, F., Natale, G., Marino, G., Ghiglieri, V., & Calabresi, P.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Agostino Gemelli University Polyclinic (IT)
- Corresponding author
- Ghiglieri, V.
- Calabresi, P.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2022-06
- Volume
- 168
- Pages
- 105697
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W4220725017
- Cited by
- 86
- References
- 146
- Citations by year
- 2026: 19 · 2025: 32 · 2024: 15 · 2023: 15 · 2022: 5
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- York University
- Ministero della Salute
- National Institutes of Health (NS045962)
- School of Medicine, New York University
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Parkinson's disease, striatum, levodopa-induced dyskinesia, basal ganglia, medium spiny neurons, synaptic dysfunction, glutamatergic neurotransmission, synaptopathy, preclinical animal models, early-stage disease
- MeSH terms
- Animals, Basal Ganglia, Corpus Striatum, Levodopa, Parkinson Disease, Neostriatum
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