Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The heroin analogue 1-methyl-4-phenylpyridinium, MPP(+), both in vitro and in vivo, produces death of dopaminergic substantia nigral cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome indistinguishable from Parkinson's disease. Similarly, a fragment of amyloid protein, Abeta(1-42), is lethal to hippocampal cells, producing recent memory deficits characteristic of Alzheimer's disease. Here we show that addition of 4 mM d-beta-hydroxybutyrate protected cultured mesencephalic neurons from MPP(+) toxicity and hippocampal neurons from Abeta(1-42) toxicity. Our previous work in heart showed that ketone bodies, normal metabolites, can correct defects in mitochondrial energy generation. The ability of ketone bodies to protect neurons in culture suggests that defects in mitochondrial energy generation contribute to the pathophysiology of both brain diseases. These findings further suggest that ketone bodies may play a therapeutic role in these most common forms of human neurodegeneration.

Original publication

DOI

10.1073/pnas.97.10.5440

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

09/05/2000

Volume

97

Pages

5440 - 5444

Keywords

1-Methyl-4-phenylpyridinium, 3-Hydroxybutyric Acid, Alzheimer Disease, Amyloid beta-Peptides, Animals, Cells, Cultured, Culture Media, Serum-Free, Embryo, Mammalian, Hippocampus, Humans, Ketone Bodies, Mesencephalon, Microtubule-Associated Proteins, Models, Neurological, Neurons, Parkinson Disease, Peptide Fragments, Rats, Tyrosine 3-Monooxygenase