Paraquat-induced intracellular Zn2+ dysregulation causes dopaminergic degeneration in the substantia nigra, but not in the striatum

Tamura, Haruna; Nishio, Ryusuke; Saeki, Nana; Katahira, Misa; Morioka, Hiroki; Tamano, Haruna; Takeda, Atsüshi

doi:10.1016/j.neuro.2022.03.010

Cited by 7 publications

(1 citation statement)

References 36 publications

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“…Since the movement disturbance and the resulting neurodegeneration were both inhibited by the co-injection of Zn 2+ chelators (ZnAF-2DA and TPEN), it was shown that these effects were caused by intracellular Zn 2+ dysregulation. The study also showed that TPEN prevented the rapid rise in nigral intracellular Zn 2+ levels that was caused by AMPA, indicating that AMPA plays a direct role in Zn 2+ inflow [99,100].…”

Section: Role Of Ampar In Parkinson's Diseasementioning

confidence: 78%

Glutamate Receptor Dysregulation and Platelet Glutamate Dynamics in Alzheimer’s and Parkinson’s Diseases: Insights into Current Medications

Gautam,

Naik,

Naik

et al. 2023

Biomolecules

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Two of the most prevalent neurodegenerative disorders (NDDs), Alzheimer’s disease (AD) and Parkinson’s disease (PD), present significant challenges to healthcare systems worldwide. While the etiologies of AD and PD differ, both diseases share commonalities in synaptic dysfunction, thereby focusing attention on the role of neurotransmitters. The possible functions that platelets may play in neurodegenerative illnesses including PD and AD are becoming more acknowledged. In AD, platelets have been investigated for their ability to generate amyloid-ß (Aß) peptides, contributing to the formation of neurotoxic plaques. Moreover, platelets are considered biomarkers for early AD diagnosis. In PD, platelets have been studied for their involvement in oxidative stress and mitochondrial dysfunction, which are key factors in the disease’s pathogenesis. Emerging research shows that platelets, which release glutamate upon activation, also play a role in these disorders. Decreased glutamate uptake in platelets has been observed in Alzheimer’s and Parkinson’s patients, pointing to a systemic dysfunction in glutamate handling. This paper aims to elucidate the critical role that glutamate receptors play in the pathophysiology of both AD and PD. Utilizing data from clinical trials, animal models, and cellular studies, we reviewed how glutamate receptors dysfunction contributes to neurodegenerative (ND) processes such as excitotoxicity, synaptic loss, and cognitive impairment. The paper also reviews all current medications including glutamate receptor antagonists for AD and PD, highlighting their mode of action and limitations. A deeper understanding of glutamate receptor involvement including its systemic regulation by platelets could open new avenues for more effective treatments, potentially slowing disease progression and improving patient outcomes.

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Section: Role Of Ampar In Parkinson's Diseasementioning

confidence: 78%