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New therapeutic strategy for Parkinson's and Alzheimer's disease.
Curr Med Chem. 2010; 17(25):2764-74.CM

Abstract

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 (Aβ) 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.

Authors+Show Affiliations

IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

20586718

Citation

Esposito, E, and S Cuzzocrea. "New Therapeutic Strategy for Parkinson's and Alzheimer's Disease." Current Medicinal Chemistry, vol. 17, no. 25, 2010, pp. 2764-74.
Esposito E, Cuzzocrea S. New therapeutic strategy for Parkinson's and Alzheimer's disease. Curr Med Chem. 2010;17(25):2764-74.
Esposito, E., & Cuzzocrea, S. (2010). New therapeutic strategy for Parkinson's and Alzheimer's disease. Current Medicinal Chemistry, 17(25), 2764-74.
Esposito E, Cuzzocrea S. New Therapeutic Strategy for Parkinson's and Alzheimer's Disease. Curr Med Chem. 2010;17(25):2764-74. PubMed PMID: 20586718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New therapeutic strategy for Parkinson's and Alzheimer's disease. AU - Esposito,E, AU - Cuzzocrea,S, PY - 2010/3/18/received PY - 2010/6/24/accepted PY - 2010/7/1/entrez PY - 2010/7/1/pubmed PY - 2011/3/8/medline SP - 2764 EP - 74 JF - Current medicinal chemistry JO - Curr Med Chem VL - 17 IS - 25 N2 - 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 (Aβ) 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. SN - 1875-533X UR - https://www.unboundmedicine.com/medline/citation/20586718/New_therapeutic_strategy_for_Parkinson's_and_Alzheimer's_disease_ DB - PRIME DP - Unbound Medicine ER -