共 140 条
New Therapeutic Strategy for Parkinson's and Alzheimer's Disease
被引:55
作者:
Esposito, E.
[2
]
Cuzzocrea, S.
[1
,2
]
机构:
[1] Univ Messina, Sch Med, Dept Clin & Expt Med & Pharmacol, I-98100 Messina, Italy
[2] IRCCS Ctr Neurolesi Bonino Pulejo, Messina, Italy
关键词:
Parkinson's disease;
Alzheimer;
glial injury;
MITOCHONDRIAL COMPLEX-I;
MONOAMINE-OXIDASE INHIBITOR;
NMDA RECEPTOR ANTAGONIST;
MILD COGNITIVE IMPAIRMENT;
IRON-REGULATORY PROTEINS;
LESIONED MARMOSET MODEL;
ALPHA-SYNUCLEIN;
NEURODEGENERATIVE DISEASES;
PROTEASOME INHIBITION;
CEREBROSPINAL-FLUID;
D O I:
10.2174/092986710791859324
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The development of potential neuroprotective therapies for neurodegenerative diseases (Parkinson's and Alzheimer's Disease) must be based on understanding their molecular and biochemical pathogenesis. Many potential pathways of neuronal cell death have been implicated in a mouse model of neurodegenerative disease, including excitotoxicity, toxicity from reactive oxygen species (superoxide anion, nitric oxide, hydroxyl radical), apoptosis (caspase-dependent and -independent pathways), necrosis and glial injury. Some agents that act on these pathways may be available for protecting the brain against chronic neurodegenerative conditions like Parkinson's and Alzheimer's disease. Drugs currently used to treat neurological disease and injuries provide temporary relief of symptoms but do not stop or slow the underlying neurodegenerative process. Restorative therapies for Parkinson's Disease are currently focused on cell replacement and administration of growth factors and small-molecule neurotrophic agents. The new experimental drugs, by contrast, target the common, underlying cause of destructive process of brain cell death. For example, p53 inhibitors attack a key protein involved in nerve cell death and represent a new strategy for preserving brain function following sudden injury or chronic disease. Analogues of pifithrin-alpha (PFT), which was shown in previous studies to inhibit p53, were designed, synthesized and tested to see whether they would work against cultured brain cells and animal models of neurodegenerative disease. Moreover, several agents based on the predominant anti-amyloid strategy, targeting amyloid-beta (A) peptide, which aggregates in the plaques that are a hallmark of Alzheimer's disease, would affect disease progression. Researchers are already making great strides in developing a vaccine for this progressive brain disorder. Immunization could offer a way to blunt or even prevent the deadly, memory-robbing disease. Here we review many of potential neuroprotective therapies, and strategies that might be suited to the development of innovative approaches that prevent degeneration and restore function in Parkinson's disease.
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页码:2764 / 2774
页数:11
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