15,762 results match your criteria: "Huntington Disease Dementia"
Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer's, Parkinson's, and ALS.
Int J Mol Sci
November 2024
Department of Anatomy, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.
Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression and limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, and genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene in these once-intractable conditions.
View Article and Find Full Text PDFFrequency and neuropathology of HTT repeat expansions in FTD/ALS: co-existence rather than causation.
J Neurol
December 2024
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, Tuebingen University Hospital, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany.
Article Synopsis
Cognitive impairment predicts medication discrepancies in Huntington's Disease: patient self-report compared to pharmacy records.
J Neurol
December 2024
Department of Neurology, Leiden University Medical Center, PO 9600, 2300RC, Leiden, The Netherlands.
Article Synopsis
Beyond Huntington's Disease - Late-Onset Chorea Caused by a Homozygous Variant in ERCC4.
Cerebellum
December 2024
Division for Neurodegenerative Diseases, Department of Neurology, Universitaetsmedizin Mannheim, University of Heidelberg, Mannheim, Germany.
Genetic alterations in the ERCC4 gene typically cause Xeroderma pigmentosum and other nucleotide excision repair disorders. Neurologic symptoms are present in some of these patients. In rare cases, ERCC4-mutations can manifest with prominent neurologic symptoms.
View Article and Find Full Text PDFImpact of somato-cognitive coordination therapy on activities of daily living in a patient with Huntington's disease.
BMJ Case Rep
December 2024
Department of Neurology and Clinical Rehabilitation, mediVR Rehabilitation Center Osaka, Toyonaka, Osaka, Japan.
Article Synopsis
- * A case report analyzed the effects of somato-cognitive coordination therapy (SCCT) on a woman in her 40s with early-stage HD, who underwent 22 sessions over 20 months using virtual reality technology.
- * Significant improvements were observed, including enhanced functional capacity and independence in daily living, with sustained results and positive effects on cognitive function and psychological well-being. SCCT could be an effective addition to HD treatment strategies.
Cognitive engagement may slow clinical progression and brain atrophy in Huntington's disease.
Sci Rep
December 2024
Cognition and Brain Plasticity Unit, Bellvitge Biomedical Research Institute - IDIBELL], L'Hospitalet de Llobregat, Barcelona, 08097, Spain.
Article Synopsis
- * A study involving 45 HD patients used the Cognitive Reserve Questionnaire and neuroimaging to assess the relationship between cognitive engagement and brain changes.
- * Findings revealed that those with higher cognitive engagement scores experienced less gray matter loss in key brain areas linked to executive function and motor control, indicating the importance of early cognitive involvement in HD management.
Protective Effects of Antcin H Isolated from Antrodia cinnamomea Against Neuroinflammation in Huntington's Disease via NLRP3 Inflammasome Inhibition.
J Neuroimmune Pharmacol
December 2024
Institute of Molecular Biology, National Chung Hsing University, No. 145 Xingda Rd., South Dist., Taichung, 402202, Taiwan.
Article Synopsis
- - Huntington's disease (HD) is a genetic neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene, leading to the accumulation of harmful mutant proteins in nerve cells.
- - The NLRP3 inflammasome plays a crucial role in inflammation and its overactivation contributes to neurodegeneration in HD; inhibiting it showed potential benefits in mice by reducing toxic inflammation and neuronal damage.
- - Antcin-H, a compound derived from the medicinal fungus Antrodia cinnamomea, was found to decrease neuroinflammation and toxicity while improving motor function and survival rates in a mouse model of HD, indicating its potential as a therapeutic option.
Shifting focus from ideality to reality: a qualitative study on how quality of life is defined by premanifest and manifest Huntington's disease gene expansion carriers.
Orphanet J Rare Dis
November 2024
Department of Public Health and Primary Care, Leiden University Medical Center, Postzone V0-P, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Article Synopsis
- Understanding quality of life (QoL) is crucial for diseases like Huntington's disease (HD), yet few studies focus on how gene expansion carriers (HDGECs) perceive their own QoL.
- This qualitative study interviewed 12 HDGECs (6 premanifest and 6 manifest) in the Netherlands to explore their definitions of QoL, revealing distinct themes for each group.
- Results showed that premanifest HDGECs focused on meaningful life concerns while manifest HDGECs dealt with adapting to reality, emphasizing the need for personalized care strategies that acknowledge the shifting perspectives of HDGECs.
Insights into RNA-mediated pathology in new mouse models of Huntington's disease.
FASEB J
December 2024
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Article Synopsis
- Two mouse models, one with translated (HD/100Q) and one with nontranslated (HD/100CAG) human mutant HTT, were created to study their effects on behavior and molecular changes over 21 months.
- Results showed both models displayed behavioral alterations and gene deregulations, with the nontranslated model exhibiting less severe impairments but notable anxiety increases due to mutant HTT RNA, suggesting its minor role in HD pathogenesis.
Roscovitine, a CDK Inhibitor, Reduced Neuronal Toxicity of mHTT by Targeting HTT Phosphorylation at S1181 and S1201 In Vitro.
Int J Mol Sci
November 2024
Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Article Synopsis
- * Research has focused on post-translational modifications of the HTT protein, with findings showing that certain modifications can reduce the toxicity of the mutant protein in cell and animal models.
- * A study identified cyclin-dependent kinases (CDKs) that influence the phosphorylation of specific serine sites on HTT, and the CDK inhibitor roscovitine demonstrated protective effects against mutant HTT toxicity in HD mice, highlighting its potential as a pre-clinical therapeutic.
Reprogrammed human lateral ganglionic eminence precursors generate striatal neurons and restore motor function in a rat model of Huntington's disease.
Stem Cell Res Ther
November 2024
Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, School of Medical Science, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Article Synopsis
- - Huntington's disease (HD) is a genetic disorder that leads to the loss of specific neurons in the brain, causing motor dysfunction, and researchers are exploring cell replacement therapies to restore neuronal function.
- - The study focuses on creating human lateral ganglionic eminence precursors (hiLGEPs) from adult human skin cells through a process called direct reprogramming, which was evaluated for its ability to differentiate into functional neurons.
- - Results showed that hiLGEPs could be successfully produced and transplanted into rats with HD-like symptoms, demonstrating their potential to survive, integrate, and contribute to neuronal function over a 14-week period.
Sensitivity and specificity of a seed amplification assay for diagnosis of multiple system atrophy: a multicentre cohort study.
Lancet Neurol
December 2024
Amprion, San Diego, CA, USA. Electronic address:
Article Synopsis
- A novel α-synuclein seed amplification assay (synSAA) was developed to differentiate misfolded α-synuclein seeds linked to multiple system atrophy (MSA) and Parkinson's disease (PD).
- The study analyzed cerebrospinal fluid (CSF) and brain samples from various clinical cohorts across multiple medical centers to assess the assay's diagnostic accuracy.
- Findings showed that brain samples with Lewy bodies were positive for synSAA, indicating potential for the assay in distinguishing between MSA and PD in diagnostic settings.
Critical role of hydrogen sulfide in the management of neurodegenerative disease.
Nitric Oxide
November 2024
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Raebareli, India. Electronic address:
Article Synopsis
- * HS acts as a neuromodulator that influences calcium levels in the brain, thus impacting memory, learning, and cognition.
- * The review highlights HS's protective effects in diseases like Alzheimer's, Parkinson's, and Huntington's, suggesting that HS donor therapy may help manage these conditions and enhance neuronal health.
More than just a number: the gut microbiota and brain function across the extremes of life.
Gut Microbes
November 2024
APC Microbiome Ireland, University College Cork, Cork, Ireland.
Article Synopsis
- Research on the gut microbiota's role in brain disorders, particularly neurodevelopmental and neurodegenerative conditions, has made significant strides in the last decade but still requires more rigorous studies to understand causation and mechanisms.
- Strong evidence now connects the gut microbiome to diseases like Alzheimer's and Parkinson's, supported by studies involving human-to-animal microbiome transplants and ongoing clinical trials.
- While advances in understanding the microbiome's impact on cognitive health, especially in conditions like autism and ADHD, are promising, there remain critical gaps in our knowledge that need to be addressed for developing targeted therapies.
Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system.
Neurobiol Dis
December 2024
Middle Tennessee State University, Biology Department, Murfreesboro, TN 37132, United States of America. Electronic address:
Huntington's Disease (HD) is a neurodegenerative disorder, part of the nine identified inherited polyglutamine (polyQ) diseases. Most commonly, HD pathophysiology manifests in middle-aged adults with symptoms including progressive loss of motor control, cognitive decline, and psychiatric disturbances. Associated with the pathophysiology of HD is the formation of insoluble fragments of the huntingtin protein (htt) that tend to aggregate in the nucleus and cytoplasm of neurons.
View Article and Find Full Text PDFQuantitative proteomic analysis using a mouse model of Lewy body dementia induced by α-synuclein preformed fibrils injection.
Front Dement
October 2024
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Article Synopsis
- The aggregation of α-synuclein in the nervous system leads to α-synucleinopathies, with Lewy body dementia (LBD) being a primary form of dementia characterized by Lewy bodies and neurites.
- Despite being the second leading cause of dementia after Alzheimer's, there is limited understanding of LBD’s pathological mechanisms and diagnostic criteria.
- The study used mass spectrometry to identify 179 proteins with significant changes post α-synuclein injection, linking several neurodegenerative pathways and suggesting a potential framework for distinguishing LBD from other dementias based on later cortical proteome changes.
Lutein, a versatile carotenoid: Insight on neuroprotective potential and recent advances.
Phytomedicine
December 2024
School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore 632014, India. Electronic address:
Article Synopsis
- * The pigment lutein has shown promise as a potential treatment for NDDs by enhancing brain development, cognitive function, and neuroplasticity while displaying neuroprotective effects against conditions like Alzheimer's and Parkinson's.
- * Lutein's protective actions include reducing oxidative stress, preventing neuroinflammation, and supporting neurogenesis, suggesting it could be a valuable natural therapeutic agent for combating NDDs.
Modulation of SNARE-dependent exocytosis in astrocytes improves neuropathology in Huntington's disease.
Dis Model Mech
November 2024
Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Article Synopsis
- * Research using BACHD mice and dnSNARE mice showed that reducing SNARE-dependent exocytosis protects against brain cell loss in the striatum but not in the cortex.
- * The study found changes in amino acid transporter expressions, with significant normalization of GAT3 levels when SNARE-dependent exocytosis was reduced, suggesting a potential therapeutic target in HD.
Decoding Nucleotide Repeat Expansion Diseases: Novel Insights from Studies.
Int J Mol Sci
November 2024
Human Translational Genomics Group, University Research Institute for Biotechnology and Biomedicine (BIOTECMED), Universidad de Valencia, 46100 Burjasot, Spain.
Article Synopsis
- - The use of Drosophila (fruit flies) has greatly advanced our understanding of nucleotide repeat expansion diseases (NREDs), leading to the successful modeling of about 15 diseases, including Huntington's and myotonic dystrophies.
- - These fly models help researchers investigate crucial disease mechanisms like protein aggregation and RNA toxicity, while also facilitating the discovery of potential treatments through chemical and genetic screenings.
- - Recent studies have incorporated advanced techniques like CRISPR to create transgenic flies and have explored lesser-known toxic mechanisms in NREDs, highlighting Drosophila's significance in ongoing research.
Neuroinflammatory Proteins in Huntington's Disease: Insights into Mechanisms, Diagnosis, and Therapeutic Implications.
Int J Mol Sci
November 2024
Guangdong Key Laboratory of Non-Human Primate Research, Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
Article Synopsis
- * The disease primarily affects specific neurons in the striatum and is associated with early activation of the immune system and neuroinflammatory responses, which are common in many neurodegenerative diseases.
- * Current research highlights the role of inflammatory proteins and immune cells (like microglia and astrocytes) in HD, indicating that targeting inflammation alongside other treatments could offer new therapeutic possibilities.
CK and LRRK2 Involvement in Neurodegenerative Diseases.
Int J Mol Sci
October 2024
Department of Chemical, Biological, Pharmaceuticals and Environmental Sciences, University of Messina, Viale Stagno d'Alcontres, 98166 Messina, Italy.
Article Synopsis
- * Genetic mutations in the LRRK2 gene are significant as they increase LRRK2 activity, disrupting neuronal autophagy and contributing to neurotoxicity and neuron death.
- * The review explores how the upregulation of casein kinase (CK) affects the AMPK pathway and contributes to disease processes in NDDs by impacting proteins associated with diseases like PD, HD, and AD, highlighting the role of kinases in their development.
Regulation of mRNA Biogenesis: The Norm and Pathology.
Int J Mol Sci
October 2024
Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya Str., 8/2, Moscow 119048, Russia.
Article Synopsis
- Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a genetic mutation that results in a toxic protein, and there is currently no effective treatment.
- Current gene therapy strategies focus on reducing levels of the harmful mutant protein and mRNA using methods like siRNA and antisense oligonucleotides, but these don't consider the variety of mRNA forms present in HD.
- The review emphasizes the importance of understanding how transcriptional regulation and known transcription factors contribute to disease progression, which may lead to new approaches for therapy by targeting natural regulatory mechanisms.
APOE4 rat model of Alzheimer's disease: sex differences, genetic risk and diet.
BMC Neurosci
November 2024
Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA.
Article Synopsis
- The ε4 allele of apolipoprotein E (ApoE ε4) is the major genetic risk factor for Alzheimer's disease (AD), and a high-fat diet increases this risk, especially in women who may experience earlier onset and quicker memory decline.
- A study using MRI examined the combined effects of ApoE ε4 and a high-fat/high-sucrose diet on brain function in male and female rats.
- Surprisingly, the study found that a high-fat diet had a more significant impact on cognitive performance and brain connectivity in male wildtype rats, overshadowing the genetic risk associated with ApoE ε4 in both sexes.
Restoring Compromised Cl in D2 Neurons of a Huntington's Disease Mouse Model Rescues Motor Disability.
J Neurosci
December 2024
Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 3G5, Canada
Huntington's disease (HD) is a progressive neurodegenerative disorder with no cure, characterized by significant neurodegeneration of striatal GABAergic medium spiny neurons (MSNs). Early stages of the disease are characterized by the loss of dopamine 2 receptor-expressing MSNs (D2 MSNs) followed by degeneration of dopamine 1 receptor-expressing MSNs (D1 MSNs), leading to aberrant basal ganglia signaling. While the early degeneration of D2 MSNs and impaired GABAergic transmission are well-documented, potassium chloride cotransporter 2 (KCC2), a key regulator of intracellular chloride (Cl), and therefore GABAergic signaling, has not been characterized in D1 and D2 MSNs in HD.
View Article and Find Full Text PDFProteomimetic polymer blocks mitochondrial damage, rescues Huntington's neurons, and slows onset of neuropathology in vivo.
Sci Adv
November 2024
Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208, USA.
Article Synopsis
- Recent research indicates that blocking the interaction between valosin-containing protein (VCP) and mutant huntingtin (mtHtt) can help prevent mitochondrial damage in Huntington's disease models.
- A newly developed protein-like polymer (PLP) has shown effectiveness in cellular and animal models, significantly inhibiting mitochondrial destruction and proving more stable than control oligopeptides.
- PLP has a remarkably longer circulation half-life (152 hours) and outperforms free peptide in efficacy tests, suggesting it could be a promising platform for developing treatments for central nervous system disorders.