Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Disruption of axonal transport may represent a final common pathway leading to neurological dysfunction in cerebral malaria (CM). Calpains are calcium (Ca2+)-activated cysteine proteases which have been implicated in axonal injury in neurological diseases of various aetiologies. In this study we examined the association between mu- and m-calpain, the specific inhibitor calpastatin, and axonal injury in post mortem brain tissue from patients who died from severe malaria. Calpains were associated with axons labelled for the beta-amyloid precursor protein that detects impaired axonal transport. Elevated levels of calpastatin were rarely observed in injured axons. There were increased numbers of neurones with mu-calpain in the nuclear compartment in severe malaria cases compared with non-neurological controls, and increased numbers of glia with nuclear mu-calpain in CM patients compared with non-CM malaria cases and non-neurological controls. There was marked redistribution of calpastatin in the sequestered Plasmodium falciparum-infected erythrocytes. Responses specific to malaria infection were ascertained following analysis of brain samples from fatal cases with acute axonal injury, HIV encephalitis, and progressive multifocal leucoencephalopathy. Our findings implicate a role for calpains in the modulation of disease progression in CM.

Original publication

DOI

10.1111/j.1365-2990.2006.00777.x

Type

Journal article

Journal

Neuropathol Appl Neurobiol

Publication Date

04/2007

Volume

33

Pages

179 - 192

Keywords

AIDS Dementia Complex, Adult, Aged, Axonal Transport, Axons, Calcium-Binding Proteins, Calpain, Endothelium, Vascular, Erythrocytes, Female, Humans, Immunohistochemistry, Leukoencephalopathy, Progressive Multifocal, Malaria, Falciparum, Male, Middle Aged, Neuroglia, Neurons