Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease

doi:10.1016/S0278-5846(01)00192-0

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 25, Issue 7, October 2001, Pages 1341-1357

https://doi.org/10.1016/S0278-5846(01)00192-0 Get rights and content

Abstract

1.
In the brains of patients with Alzheimer's disease (AD) signs of neuronal degeneration are accompanied by markers of microglial activation, inflammation, and oxidant damage. The presence of nitrotyrosine in the cell bodies of neurons in AD suggests that peroxynitrite contributes to the pathogenesis of the disease.
2.
A drug with antioxidant and anti-inflammatory activity may prevent neuronal degeneration in AD. Celastrol, a plant-derived triterpene, has these effects.
3.
In low nanomolar concentrations celastrol was found to suppress the production by human monocytes and macrophages of the pro-inflammatory cytokines TNF-α and IL-1β.
4.
Celastrol also decreased the induced expression of class II MHC molecules by microglia. In macrophage lineage cells and endothelial cells celastrol decreased induced but not constitutive NO production.
5.
Celastrol suppressed adjuvant arthritis in the rat, demonstrating in vivo anti-inflammatory activity. Low doses of celastrol administered to rats significantly improved their performance in memory, learning and psychomotor activity tests.
6.
The potent antioxidant and anti-inflammatory activities of celastrol, and its effects on cognitive functions, suggest that the drug may be useful to treat neurodegenerative diseases accompanied by inflammation, such as AD.

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Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease

Abstract

J. Neurol. Sci.

Biochem. Biophys. Res. Comm.

J. Neurosci. Meth.

Neurobiol. Aging

Biochem. Biophys. Res. Comm.

Free Radical. Biol.

Exp. Neurol.

Brain Res.

Function and Activities of NF-κB in the Immune System

Annu. Rev. Immunol.

Early and Rapid de novo Synthesis of Amyloid 3A4-Amyloid Precursor Protein (APP) in Activated Microglia Glia

Respiratory Burst in Brain Macrophages. A Flow Cytometric Study on Cultured Rat Macrophages

Appl. Neurobiol.

Murine Retroviral Neurovirulence Correlates with an Enhanced Ability of Virus to Infect Selectively, Replicate in, and Activate Resident Microglial Cells

Am. J. Pathol.

Inhibitory Effect of Di-catechol Rooperol on VCAM-I and iNOS Expression in Cytokine-stimulated Endothelium

Life Sci.

Brain Interleukin-1β in Alzheimer's Disease and Vascular Dementia

Meth. Find. Exp. Clin. Pharmacol.

Assays for Small Molecules with Immunosuppressive Activity

Some Antioxidants Inhibit in a Co-ordinate Fashion, the Production of Tumor Necrosis Factor-α, IL-1β and IL-6 by Human Peripherol Blood Mononuclear Cells

Int. Immunol.

Ultrastructure of Microglia that Phagocytose Amyloid and Microglia that Produce Beta-Amyloid Fibrils

Acta. Neuropathol.

Microglial Release of Nitric Oxide by the Synergistic Action of β-Amyloid and IFN-γ

Brain Res.