Article
Biology
Sushila A. Shenoy, Sushuang Zheng, Wencheng Liu, Yuanyi Dai, Yuanxiu Liu, Zhipeng Hou, Susumu Mori, Yi Tang, Jerry Cheng, Wenzhen Duan, Chenjian Li
Summary: Here we report the successful generation and characterization of a novel Huntington's disease mouse model BAC226Q, which exhibits HD-like phenotypes and can serve as a valuable tool for studying disease mechanisms and testing therapeutic approaches.
Article
Multidisciplinary Sciences
S. M. Ayala Mariscal, M. L. Pigazzini, Y. Richter, M. Ozel, I. L. Grothaus, J. Protze, K. Ziege, M. Kulke, M. ElBediwi, J. V. Vermaas, L. Colombi Ciacchi, S. Koppen, F. Liu, J. Kirstein
Summary: Huntington's disease is a neurodegenerative disorder caused by aggregation-prone mutant HTT protein. The trimeric chaperone complex formed by Hsc70, DNAJB1, and Apg2 can suppress and reverse the aggregation of HTTExon1Q(48) by binding to the HTT protein's poly-proline region through DNAJB1. The mutation of the conserved H244 in DNAJB1's HBM specifically affects the suppression and disaggregation of HTT fibrils, highlighting the importance of this interaction site for Huntington's disease.
NATURE COMMUNICATIONS
(2022)
Review
Neurosciences
Kirby M. Donnelly, Cevannah M. Coleman, Madison L. Fuller, Victoria L. Reed, Dayna Smerina, David S. Tomlinson, Margaret M. Panning Pearce
Summary: This article reviews the evidence for prion-like mechanisms in Huntington's disease, emphasizing the importance of mutant HTT protein in disease propagation, and discusses the potential benefits of targeting such mechanisms in search of therapeutic approaches.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
Kang-Yang Jih, Kuan-Lin Lai, Kon-Ping Lin, Yi-Chu Liao, Yi-Chung Lee
Summary: This study investigated the role of HTT repeat expansions in a Taiwanese cohort with ALS. The results showed that only one out of 410 ALS patients carried an HTT allele with 39 CAG repeats and none had HTT allele with 40 or more CAG repeats. The findings suggest that the HTT allele with 39 CAG repeats may be linked to ALS susceptibility.
JOURNAL OF THE CHINESE MEDICAL ASSOCIATION
(2023)
Article
Biochemistry & Molecular Biology
Surbhi Chaudhary, Asmita Dhiman, Anil Patidar, Himanshu Malhotra, Sharmila Talukdar, Rahul Dilawari, Gaurav Kumar Chaubey, Radheshyam Modanwal, Chaaya Iyengar Raje, Manoj Raje
Summary: Studies have shown that the cytoplasmic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) can prevent protein aggregation, maintain proteins in a soluble state, and interact with cyPrP and httQ-103.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Li Liu, Huichun Tong, Yize Sun, Xingxing Chen, Tianqi Yang, Gongke Zhou, Xiao-Jiang Li, Shihua Li
Summary: Huntington's disease (HD) is caused by an expansion of a CAG repeat in the HTT gene. HTT's exact function is still not fully understood, but previous studies have identified several interacting proteins that shed light on its function and structure. Among these proteins, HAP1 and HIP1 have been extensively studied, and recent research has found differences in their distribution in different animal brains. Understanding these species-specific variations in HTT-interacting proteins could provide crucial insights into HD development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Michael H. M. Gropp, Courtney L. Klaips, F. Ulrich Hartl
Summary: This study investigated the mechanism of aggregate pathology in Huntington's disease using a yeast model, and revealed the role of cellular vulnerability to age-dependent proteostatic decline. The optogenetic aggregation of polyQ protein bypassed the requirement of prion-forming protein for aggregate formation, shedding light on the prion-mediated oligomer formation mechanism.
Article
Multidisciplinary Sciences
Anuradha Bhattacharyya, Christopher R. Trotta, Jana Narasimhan, Kari J. Wiedinger, Wencheng Li, Kerstin A. Effenberger, Matthew G. Woll, Minakshi B. Jani, Nicole Risher, Shirley Yeh, Yaofeng Cheng, Nadiya Sydorenko, Young-Choon Moon, Gary M. Karp, Marla Weetall, Amal Dakka, Vijayalakshmi Gabbeta, Nikolai A. Naryshkin, Jason D. Graci, Thomas Tripodi, Amber Southwell, Michael Hayden, Joseph M. Colacino, Stuart W. Peltz
Summary: The authors describe the discovery of small molecule splicing modifiers that can be taken orally, cross the blood-brain barrier, and lower levels of huntingtin in a mouse model of Huntington's disease. These modifiers act by selectively modulating pre-messenger RNA splicing to reduce huntingtin expression throughout the brain and body.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Silvia Marti-Martinez, Luis M. Valor
Summary: Huntington's disease is a neurodegenerative disorder caused by abnormal expansion of CAG repeats in the Huntingtin gene. It not only affects the central nervous system but also has a peripheral component. Precise diagnosis and evaluation of therapeutic response require the use of biomarkers with prognostic value.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mohammed Khaled, Birgit Strodel, Abdallah Sayyed-Ahmad
Summary: Polyglutamine expansion in the huntingtin protein exon 1 is associated with neurodegenerative diseases. Molecular dynamics simulations revealed differences between nonpathogenic and pathogenic forms of Htt-ex1. The nonpathogenic monomer adopts a long alpha-helix, while the pathogenic monomer has a disordered polyglutamine region and forms compact structures with beta-sheets.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Neurosciences
Neha Sawant, Hallie Morton, Sudhir Kshirsagar, Arubala P. Reddy, P. Hemachandra Reddy
Summary: Huntington's disease is a fatal genetic disease involving multiple cellular changes, with therapeutic strategies focusing on reducing abnormal protein interactions and enhancing synaptic mitophagy.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Neurosciences
Subrata Pradhan, Rui Gao, Keegan Bush, Nan Zhang, Yogesh P. Wairkar, Partha S. Sarkar
Summary: Emerging evidence suggests a strong correlation between DNA repair deficiency, genome instability, and neurological diseases such as Huntington's disease. Research has shown that defective DNA repair plays a significant role in the progression of neurodegenerative diseases, and proteins linked to these diseases are involved in cellular pathways. This article focuses on the mechanisms by which the huntingtin protein helps DNA repair during transcription and how its mutations impede this process in Huntington's disease.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Kinneret Rozales, Amal Younis, Naseeb Saida, Anatoly Meller, Hodaya Goldman, Lior Kellerman, Ronit Heinrich, Shai Berlin, Reut Shalgi
Summary: This study used quantitative screens in human cells to investigate the effects of naturally-occurring DNAJ chaperone isoforms on the pathological aggregation of Huntington's disease-associated HTT-polyQ and ALS-related mutant FUS. The results showed that the aggregation of HTT-polyQ induces a cellular proteotoxic stress response, while mutant FUS aggregation leads to deteriorated proteostasis. The study also revealed complex interactions between different DNAJ isoforms and different aggregate types.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Laura Gantley, Brett W. Stringer, Vanessa M. Conn, Youichirou Ootsuka, Duncan Holds, Mark Slee, Kamelya Aliakbari, Kirsty Kirk, Rebecca J. Ormsby, Stuart T. Webb, Adrienne Hanson, He Lin, Luke A. Selth, Simon J. Conn
Summary: Trinucleotide repeat disorders are severe inherited neuromuscular and neurodegenerative disorders caused by abnormal expansion of repetitive sequences in the DNA. This study focused on a circular RNA molecule derived from non-canonical splicing of HTT pre-mRNA. The circHTT(2-6) was found to be highly expressed in the frontal cortex of HD patients and correlated with CAG repeat tract length. Overexpression of circHTT(2-6) in human cell lines resulted in phenotypic and genotypic changes resembling those observed in HD patients, suggesting a functional role in the pathophysiology of the disease.
Review
Neurosciences
Zainab Irfan, Sofia Khanam, Varnita Karmakar, Sayeed Mohammed Firdous, Bothaina Samih Ismail Abou El Khier, Ilyas Khan, Muneeb U. Rehman, Andleeb Khan
Summary: Huntington's disease is a neuro-degenerative disorder characterized by abnormal movements, cognitive and psychiatric disorders. The expansion of CAG trinucleotide in the htt gene leads to neuronal death and network degeneration in the brain, causing loss of motor coordination and muscle function.
Article
Neurosciences
Song Xue, Feng Kong, Yiying Song, Jia Liu
Summary: This study used resting-state functional magnetic resonance imaging to explore the relationship between individual's spontaneous neural activity and social interaction anxiety in a nonclinical population. The results showed that social interaction anxiety was correlated with the fractional amplitude of low-frequency fluctuations in several brain regions, and that emotional intelligence partially mediated this relationship. This study provides evidence for the neural basis of social interaction anxiety in the normal population and highlights the role of emotional intelligence in this anxiety.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Katsuyuki Yamaguchi, Takuya Yazawa
Summary: This study provides morphometric data on the development of the human medullary arcuate nucleus (AN) by examining the brains of preterm and perinatal infants. The results show that AN morphology demonstrates asymmetry and individual variability during the fetal period. The volume and neuronal number of AN increase exponentially with age, while neuronal density decreases exponentially. The AN may undergo neuron death and neuroblasts production after mid-gestation.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Zhan Zhou, Weixin Dai, Tianxiao Liu, Min Shi, Yi Wei, Lifei Chen, Yubo Xie
Summary: Studies have shown that propofol-induced neurotoxicity is caused by disruption of mitochondrial fission and fusion, leading to an energy supply imbalance for developing neurons. Healthy mitochondria released by astrocytes can migrate to compromised neurons to mitigate propofol-induced neurotoxicity, but the exact mechanisms involved still need further clarification.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
An Chen, Song Hao, Yongpeng Han, Yang Fang, Yibei Miao
Summary: This study explores the efficacy of two forms of BCI attention training games and finds that physical games may be more effective than video games. The research also offers valuable insights for future game design from a neuroscience perspective.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Lina Liu, Luran Liu, Yunting Lu, Tianyuan Zhang, Wenting Zhao
Summary: This study reveals that GDI1 serves as a potential diagnostic biomarker for AD and inhibition of GDI1 can attenuate Aβ-induced neurotoxicity. The findings offer new insights for the treatment of AD.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Zahra Gholami, Ava Soltani Hekmat, Ali Abbasi, Kazem Javanmardi
Summary: This study investigated the effects of alamandine on allodynia in a rat model and found the presence of MrgD receptors in the vlPAG and RVM regions. Microinjection of alamandine resulted in a significant increase in paw withdrawal threshold and could be blocked by an MrgD receptor antagonist. Upregulation of MrgD receptor expression following allodynia induction suggests a potential compensatory mechanism in response to pain.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Mingliang Xu, Lei Xia, Junjie Li, Yehong Du, Zhifang Dong
Summary: This study found that DHF effectively alleviates sevoflurane-induced cognitive impairment in developing mice by restoring the balance between tau O-GlcNAcylation and phosphorylation. Therefore, DHF has the potential to be a therapeutic agent for treating cognitive impairment associated with anesthetics, such as sevoflurane.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Tsubasa Mitsutake, Hisato Nakazono, Takanori Taniguchi, Hisayoshi Yoshizuka, Maiko Sakamoto
Summary: The posterior parietal cortex plays a crucial role in postural stability, and transcranial electrical stimulation of this region can modulate physical control responses. This study found that cathodal stimulation significantly decreased joint angular velocity in multiple directions, while there were no significant differences with transcranial random noise stimulation.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Xishuai Yang, Wei Zhang, Xueli Chang, Zuopeng Li, Runquan Du, Junhong Guo
Summary: This study aims to evaluate the efficacy of low-dose rituximab (RTX) in patients with muscle-specific kinase antibody positive myasthenia gravis (MuSK-MG). The results showed that low-dose RTX treatment led to significant improvements in clinical symptoms and quality of life for patients with MuSK-MG.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Jian Zhang, Shunyuan Guo, Rong Tao, Fan Wang, Yihong Xie, Huizi Wang, Lan Ding, Yuejian Shen, Xiaoli Zhou, Junli Feng, Qing Shen
Summary: This study established an Alzheimer's disease (AD) model of zebrafish induced by AlCl3 and found that marine-derived plasmalogens (Pls) could alleviate cognitive impairments of AD zebrafish by reversing athletic impairment and altering the expression levels of genes related to oxidative stress, ferroptosis, synaptic dysfunction, and apoptosis.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Lu Li, Jiaqi Ren, Qi Fang, Liqiang Yu, Jintao Wang
Summary: ICU-AW is a common and severe neuromuscular complication in critically ill patients. Electrophysiological examination is essential for accurate diagnosis and early prediction of the disease. This study aimed to establish and validate an ICU-AW predictive model in SIRS patients, providing a practical tool for early clinical prediction.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Ahmad Alipour, Roghayeh Mohammadi
Summary: The present study aimed to investigate the separate and combined effects of anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) and left dorsolateral prefrontal cortex (F3) regions on pain relief in patients with type-2 diabetes suffering from neuropathic pain (NP). The results showed that tDCS had the potential to induce pain relief in patients with type-2 diabetes suffering from NP. The mean perceived pain intensity in the posttest was lower in the M1 stimulation group than in the F3 stimulation group. However, more trials with larger sample sizes are necessary to define clinically relevant effects.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Eduardo J. Fusse, Franciele F. Scarante, Maria A. Vicente, Mariana M. Marrubia, Flavia Turcato, Davi S. Scomparin, Melissa A. Ribeiro, Maria J. Figueiredo, Tamires A. V. Brigante, Francisco S. Guimaraes, Alline C. Campos
Summary: Repeated exposure to psychosocial stress alters the endocannabinoid system and affects brain regions associated with emotional distress. Enhancing the effects of endocannabinoids through pharmacological inhibition induces an anti-stress behavioral effect, possibly mediated by the mTOR signaling pathway.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Giulia Agostoni, Luca Bischetti, Federica Repaci, Margherita Bechi, Marco Spangaro, Irene Ceccato, Elena Cavallini, Luca Fiorentino, Francesca Martini, Jacopo Sapienza, Mariachiara Buonocore, Michele Francesco D'Incalci, Federica Cocchi, Carmelo Guglielmino, Roberto Cavallaro, Marta Bosia, Valentina Bambini
Summary: This study found a general impairment in humor comprehension in individuals with schizophrenia, with mental jokes being more difficult for both patients and controls. Humor comprehension was closely associated with the patients' overall pragmatic and linguistic profile, while the association with Theory of Mind (ToM) was minimal. Another notable finding was the increased appreciation of humor in individuals with schizophrenia, who rated jokes as funnier than controls did, regardless of whether they were correctly or incorrectly completed. The funniness ratings were not predicted by any measure, suggesting a dimension of humor untied to cognition or psychopathology.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Xiuping Gong, Qi Li, Yang Liu
Summary: This study demonstrates that Sev targets CREBBP to inhibit ALG13 transcription, leading to hippocampal damage and cognitive impairment.
NEUROSCIENCE LETTERS
(2024)