Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
J Prev Alzheimers Dis ; 8(4): 534-551, 2021.
Article in English | MEDLINE | ID: mdl-34585229

ABSTRACT

Alzheimer's disease (AD) is a global health concern owing to its complexity, which often poses a great challenge to the development of therapeutic approaches. No single theory has yet accounted for the various risk factors leading to the pathological and clinical manifestations of dementia-type AD. Therefore, treatment options targeting various molecules involved in the pathogenesis of the disease have been unsuccessful. However, the exploration of various immunotherapeutic avenues revitalizes hope after decades of disappointment. The hallmark of a good immunotherapeutic candidate is not only to remove amyloid plaques but also to slow cognitive decline. In line with this, both active and passive immunotherapy have shown success and limitations. Recent approval of aducanumab for the treatment of AD demonstrates how close passive immunotherapy is to being successful. However, several major bottlenecks still need to be resolved. This review outlines recent successes and challenges in the pursuit of an AD vaccine.


Subject(s)
Alzheimer Disease/drug therapy , Alzheimer Vaccines , Antibodies, Monoclonal, Humanized/therapeutic use , Immunotherapy , Cognitive Dysfunction/prevention & control , Humans , Plaque, Amyloid/pathology
2.
Neuroscience ; 254: 379-94, 2013 Dec 19.
Article in English | MEDLINE | ID: mdl-24070629

ABSTRACT

In the previous report (Sonia Angeline et al., 2012), we showed an altered expression of protective proteins in rotenone-induced Parkinson's disease (PD)-like rat model. This model exhibited a marked attenuation in the expression of parkin, C terminus Hsp70 interacting protein (CHIP) and PARK 7 protein (DJ1) while enhanced levels of caspases and ubiquitin were seen. Herein, we confirmed the neuroprotective role of sesamol and naringenin individually on rotenone-induced rodent model of PD. Rotenone administration was given for 11days to generate the PD model (Sonia Angeline et al., 2012). From 11th day onward individual doses of sesamol (15mg/kg) and naringenin (10mg/kg) drugs were given orally to the rotenone PD rat model for 10 consecutive days. The impact of drugs markedly improved the motor skills, body weight, expression of parkin, DJ1, tyrosine hydroxylase and CHIP compared to the group treated with rotenone alone in the striatum and substantia nigra. These results were correlated with the reduction in caspase and ubiquitin levels by immunostaining and immunoblotting. Moreover, improved morphology and survivability of neurons were seen upon sesamol and naringenin treatment in the same rat PD model. Further we confirmed the efficacy of neuroprotective biomolecule administration on muscle from the above PD model and observed the restoration in muscle morphology, elevated level of parkin, DJ1, differential expression of heat shock proteins and reduced cell death. To conclude, for the first time we are demonstrating the comprehensive role of sesamol and naringenin (rotenone-induced PD model) in neuro and myoprotection that would have great clinical significance.


Subject(s)
Benzodioxoles/therapeutic use , Disease Models, Animal , Flavanones/therapeutic use , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/drug therapy , Phenols/therapeutic use , Rotenone/toxicity , Animals , Male , Parkinson Disease, Secondary/pathology , Rats , Rats, Wistar
3.
Neuroscience ; 220: 291-301, 2012 Sep 18.
Article in English | MEDLINE | ID: mdl-22710069

ABSTRACT

Rotenone is a pesticide that inhibits mitochondrial complex I activity, thus creating an environment of oxidative stress in the cell. Many studies have employed rotenone to generate an experimental animal model of Parkinson's disease (PD) that mimics and elicits PD-like symptoms, such as motor and cognitive decline. Cytoprotective proteins including parkin and heat shock proteins (HSPs) play major roles in slowing PD progression. Moreover, evidence suggests that mitochondrial dysfunction and oxidative stress-dependent apoptotic pathways contribute to dopaminergic neuron degeneration in PD. Here, rats were chronically exposed to rotenone to confirm that it causes a debilitating phenotype and various behavioral defects. We also performed histopathological examinations of nigrostriatal, cortical and cerebellar regions of rotenone-treated brain to elucidate a plausible neurodegenerative mechanism. The results of silver, tyrosine hydroxylase (TH), parkin, ubiquitin and caspase staining of brain tissue sections further validated our findings. The stress response is known to trigger HSP in response to pharmacological insult. These protective proteins help maintain cellular homeostasis and may be capable of rescuing cells from death. Therefore, we assessed the levels of different HSPs in the rotenone-treated animals. Collectively, our studies indicated the following findings in the striatum and substantia nigra following chronic rotenone exposure in an experimental PD model: (i) behavioral deficit that correlated with histopathological changes and down regulation of TH signaling, (ii) decreased levels of the cytoprotective proteins parkin, DJ1 and Hsp70 and robust expression of mitochondrial chaperone Hsp60 according to Western blot, (iii) increased immunoreactivity for caspase 9, caspase 3 and ubiquitin and decreased parkin immunoreactivity.


Subject(s)
Caspases/biosynthesis , Heat-Shock Proteins/biosynthesis , Parkinsonian Disorders , Rotenone/toxicity , Ubiquitin-Protein Ligases/biosynthesis , Uncoupling Agents/toxicity , Animals , Blotting, Western , Fluorescent Antibody Technique , Male , Mental Disorders/chemically induced , Mental Disorders/metabolism , Mental Disorders/physiopathology , Parkinsonian Disorders/metabolism , Parkinsonian Disorders/pathology , Parkinsonian Disorders/physiopathology , Rats , Rats, Wistar , Transcriptome
SELECTION OF CITATIONS
SEARCH DETAIL
...