Excessive intracellular calcium levels induce calpain activation, thereby triggering the cell death cascade. Several lines of evidence have demonstrated the neuroprotective role of the overexpression of calpain inhibitor, calpastatin. In this study, amphetamine-induced degeneration in the substantia nigra of rats was determined by evaluating the decrease in the levels of tyrosine hydroxylase phosphorylation. Amphetamine significantly decreased calpastatin levels but increased calpain levels. An induction in calpain activity was demonstrated by an increase in the formation of calpain spectrin breakdown products. The deleterious effects of amphetamine exposure were diminished in rats by pretreatment with melatonin. In addition, the effect of melatonin on calpastatin expression was investigated in human neuroblastoma SH-SY5Y cells. Melatonin was able to increase the calpastatin levels, and this effect could be blocked by luzindole, a melatonin receptor antagonist. These results demonstrate the neuroprotective ability of melatonin and its role in inducing calpastatin expression via a receptor-dependent pathway.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562346 | PMC |
| http://dx.doi.org/10.1177/1179069517719237 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
STAT3 protects dopaminergic neurons against degeneration in animal model of Parkinson's disease.
Brain Res
February 2024
Department of Neuroscience & Shriners Hospitals for Pediatric Research Center, Temple University, USA.
Introduction: Parkinson's disease (PD) is the most prevalent disorder of the basal ganglia, propagated by the degeneration of axon terminals within the striatum and subsequent loss of dopaminergic neurons in the substantia nigra (SN). Exposure of environmental neurotoxins and mutations of several mitochondrial and proteasomal genes are primarily responsible.
Methods: To determine whether signal transducer and activator of transcription 3 (STAT3) could protect dopaminergic neurons against degeneration, we first screened it in the in vitro capacity using immortalized rat dopaminergic N27 cells under 6-OHDA neurotoxicity.
Amphetamine-induced neurite injury in PC12 cells through inhibiting GAP-43 pathway.
Neurotoxicology
December 2022
Department of Anatomy, Medical College of Jinan University, Guangzhou, Guangdong Province, China. Electronic address:
Article Synopsis
- Amphetamine (AMPH) leads to the degeneration of dopamine terminals in the central nervous system, but the exact mechanisms are still unclear.
- Researchers found that AMPH reduces the levels of GAP-43, a protein important for neuron growth, in the striatum of rats and in PC12 cells, which are models for dopaminergic neurons.
- The study indicates that AMPH causes neuron damage by inhibiting the PKCβ1/GAP-43 pathway, suggesting that activation of PKC can counteract this damage and promote neuron health.
Therapeutic potential of pluripotent stem cell-derived dopaminergic progenitors in Parkinson's disease: a systematic review protocol.
Syst Rev
June 2021
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Background: Parkinson's disease (PD) is the second most common age-dependent neurodegenerative disease that causes motor and cognitive disabilities. This disease is associated with a loss of dopamine content within the putamen, which stems from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Several approved drugs are available that can effectively treat symptoms of PD.
View Article and Find Full Text PDFInvolvement of the Protein Ras Homolog Enriched in the Striatum, Rhes, in Dopaminergic Neurons' Degeneration: Link to Parkinson's Disease.
Int J Mol Sci
May 2021
Laboratory of Behavioral Neuroscience, Ceinge Biotecnologie Avanzate, 80145 Naples, Italy.
is one of the most interesting genes regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine neurotransmission. is expressed at high levels in the dorsal striatum, with a medial-to-lateral expression gradient reflecting that of both dopamine D and adenosine A receptors. transcript is also present in the hippocampus, cerebral cortex, olfactory tubercle and bulb, substantia nigra pars compacta (SNc) and ventral tegmental area of the rodent brain.
View Article and Find Full Text PDFGenetic lack of histamine upregulates dopamine neurotransmission and alters rotational behavior but not levodopa-induced dyskinesia in a mouse model of Parkinson's disease.
Neurosci Lett
June 2020
Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. Electronic address:
The brain histaminergic and dopaminergic systems closely interact, and some evidence also suggests significant involvement of histamine in Parkinson's disease (PD), where dopaminergic neurons degenerate. To further investigate histamine-dopamine interactions, particularly in the context of PD, a genetic lack of histamine and a mouse model of PD and levodopa-induced dyskinesia were here combined. Dopaminergic lesions were induced in histidine decarboxylase knockout and wildtype mice by 6-hydroxydopamine injections into the medial forebrain bundle.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!