Antibiotic for Huntington’s disease?
Aiming to slow Huntington’s disease, Robert M. Friedlander of Brigham and Women’s Hospital in Boston has tested inhibitors of caspases, a family of enzymes that cells produce in their death throes (SN: 5/29/99, p. 351). An old antibiotic may offer an alternative: In mice genetically engineered to develop an illness similar to the neurodegenerative disease, the drug significantly delays the onset of symptoms and death, Friedlander and his colleagues report in the July Nature Medicine.
The Harvard Gazette, Old-Line Antibiotic Seen to Save Neurons
Findings may be applied to stroke, neurodegenerative disease
Developed as an antibiotic 30 years ago, a drug called minocycline was later discovered to ease acne, rheumatoid arthritis, and other inflammatory conditions. A few years ago, it was shown to slow and even limit the neuronal damage caused by stroke and Huntington’s disease in mice.
Untangling huntingtin’s mysteries
We have reached a critical juncture in the search for a cure for Huntington disease (HD), and nowhere was this more apparent than in Boston recently at the annual research conference sponsored by the Hereditary Disease Foundation (HDF, http://www.hdfoundation.org), Huntington Disease 2000: Changes, Advances and Good News (CAG). The symposium provided a forum for the expanding community of Huntington researchers to share their latest results.
ICE, neuronal apoptosis and neurodegeneration
Significant progress has recently occurred in the understanding of the molecular mechanisms mediating vertebrate programmed cell death, or apoptosis. New advances in this field have stemmed from the identification of ICE (caspase-1) as the founding member of the mammalian caspase cell death family.
Hunting down Huntington’s disease
Melatonin inhibits the caspase-1/cytochrome c/caspase-3 cell death pathway, inhibits MT1 receptor loss and delays disease progression in a mouse model of amyotrophic lateral sclerosis
Caspase-mediated cell death contributes to the pathogenesis of motor neuron degeneration in the mutant SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS), along with other factors such as inflammation and oxidative damage. By screening a drug library, we found that melatonin, a pineal hormone, inhibited cytochrome c release in purified mitochondria and prevented cell death in cultured neurons. In this study, we evaluated whether melatonin would slow disease progression in SOD1G93A mice.
Complement in neuroprotection and neurodegeneration
Acute neurodegeneration is associated with high morbidity and mortality, and there are few effective treatments. Inflammation is central to the process of neuronal death, yet the roles of the complement cascade in this process have proven to be complex and hard to unravel.
Huntingtin inhibits caspase‐3 activation
Huntington’s disease results from a mutation in the HD gene encoding for the protein huntingtin. The function of huntingtin, although beginning to be elucidated, remains largely unclear.
Caspases in Huntington’s Disease
Huntington’s disease (HD) is an autosomal dominant condition, resulting from a mutation in huntingtin (htt). Htt is a novel protein, and its normal function is at present not well understood. Nuclear translocation of mutant htt in vitro up-regulates expression of the cell death gene caspase-1.
Inhibitors of Cytochrome c Release with Therapeutic Potential for Huntington’s Disease
Release of mitochondrial cytochrome c resulting in downstream activation of cell death pathways has been suggested to play a role in neurologic diseases featuring cell death. However, the specific biologic importance of cytochrome c release has not been demonstrated in Huntington’s disease (HD).