Article
Multidisciplinary Sciences
Julia E. Gerson, Hunter Linton, Jiazheng Xing, Alexandra B. Sutter, Fayth S. Kakos, Jaimie Ryou, Nyjerus Liggans, Lisa M. Sharkey, Nathaniel Safren, Henry L. Paulson, Magdalena I. Ivanova
Summary: Brain-expressed ubiquilins UBQLNs 1, 2 and 4 play crucial roles in protein homeostasis and neurodegenerative diseases, with recent research showing differences in aggregation propensity among them, with UBQLN4 exhibiting heightened aggregation propensity.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Shun Kubota, Hiroshi Doi, Shigeru Koyano, Kenichi Tanaka, Hiroyasu Komiya, Atsuko Katsumoto, Shingo Ikeda, Shunta Hashiguchi, Haruko Nakamura, Ryoko Fukai, Keita Takahashi, Misako Kunii, Mikiko Tada, Hideyuki Takeuchi, Fumiaki Tanaka
Summary: The study identified small glutamine-rich tetratricopeptide repeat-containing protein alfa (SGTA) as an aggregate-interacting protein in neurodegenerative diseases. SGTA was found to interact with polyQ aggregates and reduce their accumulation, suggesting a potential role as a modifier in the molecular pathological mechanisms of various diseases.
Article
Biotechnology & Applied Microbiology
Ana Vasconcelos-Ferreira, Ines Morgado Martins, Diana Lobo, Dina Pereira, Miguel M. Lopes, Rosario Faro, Sara M. Lopes, Dineke Verbeek, Thorsten Schmidt, Clevio Nobrega, Luis Pereira de Almeida
Summary: This study investigated the transcriptional modifications of the autophagy pathway in Machado-Joseph disease (MJD) and found that autophagy is impaired at the transcriptional level in this disease. Restoring the levels of autophagy activating kinases 1 and 2 (ULK1 and ULK2) significantly improved motor performance.
Article
Clinical Neurology
Yi-Chu Liao, Cheng-Yu Wei, Fu-Pang Chang, Ying-Tsen Chou, Shao-Lun Hsu, Chih-Ping Chung, Takeshi Mizuguchi, Naomichi Matsumoto, Shaw-Fang Yet, Yi-Chung Lee
Summary: This study found that GGC repeat expansion in the NOTCH2NLC gene may contribute to cerebral small vessel disease (cSVD). A screening of 197 patients with unresolved vascular leukoencephalopathy revealed that 6 patients carried the GGC repeat expansion, and these patients exhibited clinical and neuroimaging features similar to cSVD. Therefore, the presence of NIID should be considered in patients presenting with cSVD.
Article
Biology
Jesus G. Galaz-Montoya, Sarah H. Shahmoradian, Koning Shen, Judith Frydman, Wah Chiu
Summary: Recent research using cryo-electron tomography and subtomogram averaging revealed that mHTT exon 1 and polyQ-only aggregates in vitro are structurally heterogeneous and filamentous, with thin filaments and large sheet regions. Moreover, a prevalent subpopulation of filaments exhibiting a lumpy slab morphology in both types of aggregates was observed, supporting the polyQ core model. These findings provide a basis for future cryoET studies of various aggregated mHTT and polyQ constructs.
COMMUNICATIONS BIOLOGY
(2021)
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)
Article
Clinical Neurology
Yasuo Miki, Kosuke Kamata, Shintaro Goto, Hirotake Sakuraba, Fumiaki Mori, Kazufumi Yamagata, Hiroshi Kijima, Shinsaku Fukuda, Koichi Wakabayashi
Summary: In adult neuronal intranuclear inclusion disease (NIID), both neurons and glial cells harbor intranuclear inclusions, which can also be found in the peripheral autonomic nervous system, visceral organs, and skin. This study reports a case of NIID in a 78-year-old Japanese male who exhibited mild tremors but did not show typical radiographic abnormalities. Pathological analysis revealed that neuronal intranuclear inclusions were particularly frequent in the hippocampal formation, while glial intranuclear inclusions were barely evident in the affected regions. The case also had an immunohistochemical profile differing from that of typical adult NIID.
Article
Neurosciences
Masanori Kurihara, Tatsuo Mano, Fumihiro Eto, Ikuko Yao, Kenichiro Sato, Gaku Ohtomo, Taro Bannai, Shota Shibata, Hiroyuki Ishiura, Masako Ikemura, Tomoyasu Matsubara, Maho Morishima, Yuko Saito, Shigeo Murayama, Tatsushi Toda, Mitsutoshi Setou, Atsushi Iwata
Summary: Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease with eosinophilic hyaline intranuclear inclusions as a pathological hallmark. CGG repeat expansions in NOTCH2NLC have been identified in most East Asian patients with NIID. In this study, proteomic analysis was performed on nuclei with p62-positive inclusions to identify candidate proteins involved in NIID pathophysiology. The results revealed increased levels of RNA-binding proteins in nuclei with p62-positive inclusions, which may contribute to the understanding of NIID pathophysiology.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Clemence Labasse, Guy Brochier, Ana-Lia Taratuto, Bruno Cadot, John Rendu, Soledad Monges, Valerie Biancalana, Susana Quijano-Roy, Mai Thao Bui, Anais Chanut, Angeline Madelaine, Emmanuelle Lacene, Maud Beuvin, Helge Amthor, Laurent Servais, Yvan de Feraudy, Marcela Erro, Maria Saccoliti, Osorio Abath Neto, Julien Faure, Beatrice Lannes, Vincent Laugel, Sandra Coppens, Fabiana Lubieniecki, Ana Buj Bello, Nigel Laing, Teresinha Evangelista, Jocelyn Laporte, Johann Bohm, Norma B. Romero
Summary: This study expands the genetic and morphological spectrum of severe ACTA1-related nemaline myopathy, highlights the enlargement of the perinuclear space as an ultrastructural hallmark, and indicates a potential genotype/phenotype correlation.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Rajasekhar Kolla, Pushparathinam Gopinath, Jonathan Ricci, Andreas Reif, Iman Rostami, Hilal A. Lashuel
Summary: Huntington's disease is caused by the expansion of a polyglutamine repeat in the huntingtin protein, leading to protein aggregation and formation of inclusions. Research on mutant N-terminal Htt fragments reveals that post-translational modifications and structured domains beyond Httex1 influence aggregation mechanisms. Different N-terminal fragments exhibit distinct aggregation mechanisms, highlighting the need for tailored antiaggregation strategies and further studies on how Htt fragments interact and impact disease progression.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Geriatrics & Gerontology
Yueqi Liu, Hao Li, Xuan Liu, Bin Wang, Hao Yang, Bo Wan, Miao Sun, Xingshun Xu
Summary: Due to the high clinical heterogeneity, diagnosing neuronal intranuclear inclusion disease (NIID) can be challenging. This review summarizes the clinical symptoms in different systems and proposes the core triad symptoms in the central nervous system as an important clue for diagnosis. Recent studies have identified the cause of NIID as expanded GGC repeats in the NOTCH2NLC gene. Additionally, inflammation could be a target for therapeutic interventions in NIID.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Nathan Riguet, Anne-Laure Mahul-Mellier, Niran Maharjan, Johannes Burtscher, Marie Croisier, Graham Knott, Janna Hastings, Alice Patin, Veronika Reiterer, Hesso Farhan, Sergey Nasarov, Hilal A. Lashuel
Summary: This study investigates the ultrastructural and biochemical properties of huntingtin cytoplasmic and nuclear inclusions, showing that they form via distinct mechanisms and exert their toxicity via different pathways. The findings provide insight into the complex processes of Htt inclusion formation and maturation, involving polyQ-dependent aggregation, sequestration of lipids and proteins related to HD pathways, accumulation of dysfunctional organelles, and impairment of protein quality control mechanisms. Nuclear and cytoplasmic Htt inclusions exhibit distinct compositions and properties, suggesting different mechanisms of aggregation and toxicity.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Midori Suzuki, Shunichi Moriya, Sayaka Kobayashi, Yoshimi Nishijima, Takaaki Fujii, Hayato Ikota, Hideaki Yokoo, Masanao Saio
Summary: The study revealed that the appearance rate of NI in cytological specimens is positively correlated with the nuclear area and perimeter, and negatively correlated with nuclear roundness. These results are consistent regardless of the presence of BRAFV600E mutation, demonstrating the utility of cytological specimens in computer-assisted image analysis.
Article
Medicine, General & Internal
Tomoya Kawazoe, Shinsuke Tobisawa, Keizo Sugaya, Akinori Uruha, Kazuhito Miyamoto, Takashi Komori, Yu-ichi Goto, Ichizo Nishino, Hiroshi Yoshihashi, Takeshi Mizuguchi, Naomichi Matsumoto, Naohiro Egawa, Akihiro Kawata, Eiji Isozaki
Summary: We report a case of MERRF with a novel variant in MT-TC, characterized by progressive myoclonic epilepsy with optic atrophy and peripheral neuropathy. Intracellular inclusions were found in the skin biopsy, but no mutations were identified in known causative genes for diseases associated with intracellular inclusions. The association between these inclusions and the newly identified MERRF-associated variant remains unclear.
Article
Chemistry, Medicinal
Shakir Ahamad, Shahnawaz A. Bhat
Summary: Huntington's disease is a neuro-degenerative disorder caused by a mutation in the huntingtin gene. New research has led to the discovery of small-molecule therapeutics that show promise for treating this disease. This article summarizes the development of these therapeutics, including their structure, therapeutic effects, and mechanisms of action. Additionally, the key drivers of Huntington's disease pathogenesis are highlighted to aid in the design of effective treatments.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Nutrition & Dietetics
Shuya Kasai, Hiromi Yamazaki, Kunikazu Tanji, Mate Janos Engler, Tomoh Matsumiya, Ken Itoh
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
(2019)
Article
Neurosciences
Le Duy Do, Stephanie L. Gupton, Kunikazu Tanji, Joubert Bastien, Sabine Brugiere, Yohann Coute, Isabelle Quadrio, Veronique Rogemond, Nicole Fabien, Virginie Desestret, Jerome Honnorat
Article
Clinical Neurology
Tomoya Kon, Fumiaki Mori, Akira Arai, Yasuo Miki, Kunikazu Tanji, Hidekachi Kurotaki, Masahiko Tomiyama, Koichi Wakabayashi
Article
Clinical Neurology
Kunikazu Tanji, Yasuo Miki, Fumiaki Mori, Tomoya Kon, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
Article
Biochemistry & Molecular Biology
Seigo Usuki, Noriko Tamura, Tomohiro Tamura, Kunikazu Tanji, Daisuke Mikami, Katsuyuki Mukai, Yasuyuki Igarashi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Clinical Neurology
Tomoya Kon, Fumiaki Mori, Yoshinobu Oyama, Kunikazu Tanji, Tamaki Kimura, Shirushi Takahashi, Koichi Wakabayashi
Article
Clinical Neurology
Fumiaki Mori, Yasuo Miki, Tomoya Kon, Kunikazu Tanji, Koichi Wakabayashi
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2019)
Article
Neurosciences
Fumiaki Mori, Mari Tada, Tomoya Kon, Yasuo Miki, Kunikazu Tanji, Hidekachi Kurotaki, Masahiko Tomiyama, Tomohiko Ishihara, Osamu Onodera, Akiyoshi Kakita, Koichi Wakabayashi
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2019)
Article
Neurosciences
Chihiro Sato, Kunikazu Tanji, Shuji Shimoyama, Mitsuru Chiba, Misaki Mikami, Shuhei Koeda, Koshi Sumigawa, Kazuki Akahira, Junko Yamada
Article
Cell Biology
Seigo Usuki, Yoshiaki Yasutake, Noriko Tamura, Tomohiro Tamura, Kunikazu Tanji, Takashi Saitoh, Yuta Murai, Daisuke Mikami, Kohei Yuyama, Kenji Monde, Katsuyuki Mukai, Yasuyuki Igarashi
Article
Genetics & Heredity
Hiromi Yamazaki, Shuya Kasai, Junsei Mimura, Peng Ye, Atsushi Inose-Maruyama, Kunikazu Tanji, Koichi Wakabayashi, Seiya Mizuno, Fumihiro Sugiyama, Satoru Takahashi, Tsubasa Sato, Taku Ozaki, Douglas R. Cavener, Masayuki Yamamoto, Ken Itoh
Article
Biochemistry & Molecular Biology
Kunikazu Tanji, Fumiaki Mori, Fumiyuki Shirai, Takehiro Fukami, Hiroyuki Seimiya, Jun Utsumi, Akiyoshi Kakita, Koichi Wakabayashi
Summary: Research has shown that tankyrase inhibitors can suppress the formation of TDP-43 protein aggregates and reduce the levels of tankyrase protein in neuronal cytoplasmic inclusions, potentially protecting against TDP-43 toxicity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Clinical Neurology
Yasuo Miki, Kunikazu Tanji, Kana Shinnai, Makoto T. Tanaka, Firat Altay, Sandrine C. Foti, Catherine Strand, Takanori Sasaki, Tomoya Kon, Shuji Shimoyama, Tomonori Furukawa, Haruo Nishijima, Hiromi Yamazaki, Yasmine T. Asi, Conceicao Bettencourt, Zane Jaunmuktane, Mari Tada, Fumiaki Mori, Hiroki Mizukami, Masahiko Tomiyama, Hilal A. Lashuel, Tammaryn Lashley, Akiyoshi Kakita, Helen Ling, Andrew J. Lees, Janice L. Holton, Thomas T. Warner, Koichi Wakabayashi
Summary: This study investigated how abnormal alpha-synuclein in the hippocampus leads to memory impairment in multiple system atrophy (MSA). The results suggest that increased alpha-synuclein oligomers may be a pathological cause of memory impairment in MSA.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Meeting Abstract
Clinical Neurology
Kunikazu Tanji, Yasuo Miki, Fumiaki Mori, Yoshikazu Nikaido, Hidemi Narita, Akiyoshi Kakita, Hitoshi Tkahashi, Koichi Wakabayashi
Meeting Abstract
Clinical Neurology
F. Mori, Y. Miki, Y. Seino, K. Tanji, T. Yoshizawa, H. Kijima, M. Shoji, K. Wakabayashi
