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Psychopharmacological neuroprotection in neurodegenerative disease: assessing the preclinical data.
J Neuropsychiatry Clin Neurosci. 2010 Winter; 22(1):8-18.JN

Abstract

This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer's and Parkinson's diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided.

Authors+Show Affiliations

Mercer University Center for Translational Studies in Alzheimer's, Parkinson's, and Neurodegenerative Diseases, Macon, GA 31201, USA. eclbgnp@earthlink.netNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

20160205

Citation

Lauterbach, Edward C., et al. "Psychopharmacological Neuroprotection in Neurodegenerative Disease: Assessing the Preclinical Data." The Journal of Neuropsychiatry and Clinical Neurosciences, vol. 22, no. 1, 2010, pp. 8-18.
Lauterbach EC, Victoroff J, Coburn KL, et al. Psychopharmacological neuroprotection in neurodegenerative disease: assessing the preclinical data. J Neuropsychiatry Clin Neurosci. 2010;22(1):8-18.
Lauterbach, E. C., Victoroff, J., Coburn, K. L., Shillcutt, S. D., Doonan, S. M., & Mendez, M. F. (2010). Psychopharmacological neuroprotection in neurodegenerative disease: assessing the preclinical data. The Journal of Neuropsychiatry and Clinical Neurosciences, 22(1), 8-18. https://doi.org/10.1176/appi.neuropsych.22.1.8
Lauterbach EC, et al. Psychopharmacological Neuroprotection in Neurodegenerative Disease: Assessing the Preclinical Data. J Neuropsychiatry Clin Neurosci. 2010;22(1):8-18. PubMed PMID: 20160205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Psychopharmacological neuroprotection in neurodegenerative disease: assessing the preclinical data. AU - Lauterbach,Edward C, AU - Victoroff,Jeff, AU - Coburn,Kerry L, AU - Shillcutt,Samuel D, AU - Doonan,Suzanne M, AU - Mendez,Mario F, PY - 2010/2/18/entrez PY - 2010/2/18/pubmed PY - 2010/5/21/medline SP - 8 EP - 18 JF - The Journal of neuropsychiatry and clinical neurosciences JO - J Neuropsychiatry Clin Neurosci VL - 22 IS - 1 N2 - This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer's and Parkinson's diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided. SN - 1545-7222 UR - https://www.unboundmedicine.com/medline/citation/20160205/Psychopharmacological_neuroprotection_in_neurodegenerative_disease:_assessing_the_preclinical_data_ L2 - https://neuro.psychiatryonline.org/doi/full/10.1176/jnp.2010.22.1.8?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -