Huntington disease is a highly disabling neurodegenerative disease characterized by psychiatric, cognitive, and motor deficits. The causal genetic mutation in huntingtin (Htt, also known as IT15), located on chromosome 4p16.3, leads to an expansion of a triplet coding for polyglutamine. The expansion is invariably associated with the disease when >39 repeats. Htt encodes for the protein huntingtin (HTT), which carries out many essential biological functions in the cell, in particular in the nervous system. The precise mechanism of toxicity is not known. Based on a one-gene-one-disease framework, the prevailing hypothesis ascribes toxicity to the universal aggregation of HTT. However, the aggregation process into mutant huntingtin (mHTT) is associated with a reduction of the levels of wild-type HTT. A loss of wild-type HTT may plausibly be pathogenic, contributing to the disease onset and progressive neurodegeneration. Moreover, many other biological pathways are altered in Huntington disease, such as in the autophagic system, mitochondria, and essential proteins beyond HTT, potentially explaining biological and clinical differences among affected individuals. As one gene does not mean one disease, future efforts at identifying specific Huntington subtypes are important to design biologically tailored therapeutic approaches that correct the corresponding biological pathways-rather than continuing to exclusively target the common denominator of HTT aggregation for elimination.
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http://dx.doi.org/10.1016/B978-0-323-85555-6.00003-5 | DOI Listing |
Expert Opin Ther Pat
December 2024
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Introduction: Neuroinflammation is correlated to neurodegenerative diseases like Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Huntington Disease (HD) and Parkinson's disease (PD). A lot of recent research and patents are focused on the design and synthesis of arachidonic acid Lipoxygenase (ALOX) inhibitors for the treatment of neurodegenerative diseases.
Areas Covered: The survey covers natural products, synthesis, hybrids, and assessments of biological effects in biological studies as ALOX inhibitors.
Neurobiol Dis
December 2024
Department of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada. Electronic address:
Background: Altered balance between striatal direct and indirect pathways contributes to early motor, cognitive and psychiatric symptoms in Huntington disease (HD). While degeneration of striatal D2-type dopamine receptor (D2)-expressing indirect pathway medium spiny neurons (iMSNs) occurs prior to that of D1-type dopamine receptor (D1)-expressing direct pathway neurons, altered corticostriatal synaptic function precedes degeneration. D2-mediated signaling on iMSNs reduces their excitability and promotes endocannabinoid (eCB) synthesis, suppressing glutamate release from cortical afferents.
View Article and Find Full Text PDFJ Neurosci Res
December 2024
Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, School of Medical Science, Centre for Brain Research, University of Auckland, Auckland, New Zealand.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder traditionally characterized by the selective loss of medium spiny neurons in the basal ganglia. However, it has become apparent that white matter injury and oligodendrocyte dysfunction precede the degeneration of medium spiny neurons, garnering interest as a key pathogenic mechanism of HD. Oligodendrocytes are glial cells found within the central nervous system involved in the production of myelin and the myelination of axons.
View Article and Find Full Text PDFBrain Commun
November 2024
Department of Neurodegenerative Disease, Huntington's Disease Centre, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in the huntingtin (HTT) protein. The mutant CAG repeat is unstable and expands in specific brain cells and peripheral tissues throughout life. Genes involved in the DNA mismatch repair pathways, known to act on expansion, have been identified as genetic modifiers; therefore, it is the rate of somatic CAG repeat expansion that drives the age of onset and rate of disease progression.
View Article and Find Full Text PDFCureus
November 2024
Internal Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, USA.
Prosthetic joint infection (PJI), caused by Streptococcus bovis group (SBG), is uncommon and related to colorectal cancer. We present here a case of an 84-year-old male who had a past medical history of chronic obstructive pulmonary disease (COPD), congestive heart failure, pulmonary arterial hypertension, iron deficiency anemia, chronic kidney disease, diabetes mellitus, gout, hypertension, bilateral knee replacement with left knee pain and swelling. We initially suspected gout and treated him with prednisolone, but it did not relieve him.
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