| Title |
Neuroprotective Effects of Temsirolimus in Animal Models of Parkinson’s Disease
|
|---|---|
| Published in |
Molecular Neurobiology, March 2017
|
| DOI | 10.1007/s12035-017-0496-4 |
| Pubmed ID | |
| Authors |
Rosalba Siracusa, Irene Paterniti, Marika Cordaro, Rosalia Crupi, Giuseppe Bruschetta, Michela Campolo, Salvatore Cuzzocrea, Emanuela Esposito |
| Abstract |
Parkinson's disease (PD) is a disorder caused by degeneration of dopaminergic neurons. At the moment, there is no cure. Recent studies have shown that autophagy may have a protective function against the advance of a number of neurodegenerative diseases. Temsirolimus is an analogue of rapamycin that induces autophagy by inhibiting mammalian target of rapamycin complex 1. For this purpose, in the present study we investigated the neuroprotective effects of temsirolimus (5 mg/kg intraperitoneal) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced (MPTP) neurotoxicity in in vivo model of PD. At the end of the experiment, brain tissues were processed for histological, immunohistochemical, Western blot, and immunofluorescent analysis. Treatment with temsirolimus significantly ameliorated behavioral deficits, increased the expression of specific markers of PD such as tyrosine hydroxylase, dopamine transporter, as well as decreased the upregulation of α-synuclein in the substantia nigra after MPTP induction. Furthermore, Western blot and immunohistochemistry analysis showed that temsirolimus administration significantly increased autophagy process. In fact, treatment with temsirolimus maintained high Beclin-1, p62, and microtubule-associated protein 1A/1B-light chain 3 expression and inhibited the p70S6K expression. In addition, we showed that temsirolimus has also anti-inflammatory properties as assessed by the significant inhibition of the expression of mitogen-activated protein kinases such as p-JNK, p-p38, and p-ERK, and the restored levels of neurotrophic factor expression such as BDNF and NT-3. On the basis of this evidence, we clearly demonstrate that temsirolimus is able to modulate both the autophagic process and the neuroinflammatory pathway involved in PD, actions which may underlie its neuroprotective effect. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 33% |
| United Kingdom | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 2% |
| Unknown | 42 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 16% |
| Student > Ph. D. Student | 6 | 14% |
| Student > Master | 4 | 9% |
| Student > Bachelor | 3 | 7% |
| Other | 2 | 5% |
| Other | 5 | 12% |
| Unknown | 16 | 37% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 14% |
| Agricultural and Biological Sciences | 5 | 12% |
| Neuroscience | 5 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 7% |
| Medicine and Dentistry | 3 | 7% |
| Other | 4 | 9% |
| Unknown | 17 | 40% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 April 2017.
All research outputs
#3,090,927
of 22,962,258 outputs
Outputs from Molecular Neurobiology
#550
of 3,477 outputs
Outputs of similar age
#58,982
of 308,778 outputs
Outputs of similar age from Molecular Neurobiology
#13
of 108 outputs
Altmetric has tracked 22,962,258 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,477 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has done well, scoring higher than 82% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 308,778 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 108 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.