Inhibition of mitochondrial protein import by mutant huntingtin

Chiari malformation, an anomaly of the posterior cranial
fossa, also known as Arnold–Chiari malformation, was described in autopsies
by Hans Chiari, an Austrian pathologist, in 1891. He defined four
distinct anatomical configurations in which the cerebellar tonsils (the most caudal
part of the cerebellum) protruded below the lower margin of the foramen magnum.1

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.

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.

Hunting down Huntington’s disease

Advances in RNA interference – Delivery and Allele-Specific Silencing

Many researchers now believe that the cure for Huntington’s Disease will involve
silencing the mutant gene. The HD community was electrified by Dr. Beverly
Davidson’s groundbreaking research with a mouse model of spinocerebellar ataxia,
another autosomal dominant genetic neurodegenerative disorder in 2004 and again in
2005 when she successfully silenced the HD gene in the N171-82Q mouse model of
Huntington’s Disease using RNA interference.

Enzyme Suggests Way to Halt Huntington’s

By tinkering with an enzyme in the brain cells of mice, medical researchers may have opened the door to a treatment for Huntington’s disease, an as-yet-untreatable progressive brain disorder. The findings, which appear in tomorrow’s issue of Nature, show that an enzyme involved in cellular suicide plays an unexpected role in the disease.

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).

Sequential activation of individual caspases, and of alterations in Bcl-2 proapoptotic signals in a mouse model of Huntington’s disease

Caspases play an important role in neurodegeneration in Huntington’s disease (HD). Members of the Bcl-2 family are critical modulators of terminal cell death pathways. However, alterations of Bcl-2 family members and their functional role in an in vivo model of HD have not been documented.