Article
Oncology
Yusei Yamada, Madoka Fukaura-Nishizawa, Asami Nishiyama, Akira Ishii, Tatsuya Kawata, Aina Shirakawa, Mayuko Tanaka, Yuki Kondo, Toru Takeo, Naomi Nakagata, Toru Miwa, Hiroki Takeda, Yorihisa Orita, Keiichi Motoyama, Taishi Higashi, Hidetoshi Arima, Takahiro Seki, Yuki Kurauchi, Hiroshi Katsuki, Katsumi Higaki, Kentaro Minami, Naoki Yoshikawa, Ryuji Ikeda, Muneaki Matsuo, Tetsumi Irie, Yoichi Ishitsuka
Summary: This study investigates the relationship between the formation of cyclodextrin (CD) and unesterified cholesterol (UC) complexes and their therapeutic effectiveness. The findings suggest that the solubility and molecular mechanisms of CD influence the formation and complexation capability of these complexes. The ability of CD derivatives to form 1:1 and 2:1 complexes is correlated with their therapeutic efficacy and toxicity, respectively. These findings highlight the importance of optimizing the molecular structure of CDs to overcome current treatment dilemmas.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Yusei Yamada, Madoka Fukaura-Nishizawa, Asami Nishiyama, Akira Ishii, Tatsuya Kawata, Aina Shirakawa, Mayuko Tanaka, Yuki Kondo, Toru Takeo, Naomi Nakagata, Toru Miwa, Hiroki Takeda, Yorihisa Orita, Keiichi Motoyama, Taishi Higashi, Hidetoshi Arima, Takahiro Seki, Yuki Kurauchi, Hiroshi Katsuki, Katsumi Higaki, Kentaro Minami, Naoki Yoshikawa, Ryuji Ikeda, Muneaki Matsuo, Tetsumi Irie, Yoichi Ishitsuka
Summary: This study found that cyclodextrins can be used to treat Niemann-Pick disease type C (NPC), but concerns about ototoxicity exist. By optimizing the molecular structure of cyclodextrins, this study suggests a way to overcome this dilemma.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Insung Kang, Je Min Yoo, Donghoon Kim, Juhee Kim, Myung Keun Cho, Seung-Eun Lee, Dong Jin Kim, Byung-Chul Lee, Jin Young Lee, Jae-Jun Kim, Nari Shin, Soon Won Choi, Young-Ho Lee, Han Seok Ko, Seokmin Shin, Byung Hee Hong, Kyung-Sun Kang
Summary: Graphene quantum dots (GQDs) show promise as a potential therapeutic agent for Niemann-Pick disease type C (NPC) by reducing cholesterol aggregation in lysosomes, promoting autophagy, and inhibiting Purkinje cell loss in the cerebellum. Their ability to alleviate impaired functions in NPC highlights the potential of GQDs for treating NPC and related disorders.
Article
Medicine, General & Internal
Jacinda Chen, Rajesh Kumar Soni, Yimeng Xu, Sabrina Simoes, Feng-Xia Liang, Laura DeFreitas, Robert Hwang Jr, Jorge Montesinos, Joseph H. Lee, Estela Area-Gomez, Renu Nandakumar, Badri Vardarajan, Catherine Marquer
Summary: By analyzing the LE/Lys in the brains of JNCL patients, it was found that the accumulation of cholesterol in JNCL samples was comparable to that in NPC samples, suggesting that JNCL is a lysosomal cholesterol storage disorder. In addition, JNCL and NPC disease share pathogenic pathways, and treatments for NPC disease may be beneficial for JNCL patients.
Review
Biochemistry & Molecular Biology
Antonietta Bernardo, Chiara De Nuccio, Sergio Visentin, Alberto Martire, Luisa Minghetti, Patrizia Popoli, Antonella Ferrante
Summary: Niemann-Pick type C (NPC) disease is a neurovisceral disorder that mainly affects the liver and brain, caused by mutations in genes coding for proteins involved in cholesterol transport. NPC leads to the accumulation of unesterified cholesterol in lysosomes, affecting mitochondrial function and leading to neurodegeneration and myelin defects in the brain. Emerging pharmacological strategies targeting A(2A) adenosine receptor stimulation show promise for NPC therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Developmental Biology
Wei-Chia Tseng, Ana J. Johnson Escauriza, Chon-Hwa Tsai-Morris, Benjamin Feldman, Ryan K. Dale, Christopher A. Wassif, Forbes D. Porter
Summary: NPC is a rare, fatal neurodegenerative lysosomal disease caused by mutations in NPC1 or NPC2, resulting in the accumulation of cholesterol and other lipids in the lysosome and reduction in cellular cholesterol bioavailability.
Article
Multidisciplinary Sciences
Ting-Ting Chu, Xintao Tu, Kun Yang, Jianjun Wu, Joyce J. Repa, Nan Yan
Summary: This study identifies a cGAS- and cGAMP-independent mode of STING activation that affects neuropathology and provides a therapeutic target for the treatment of Niemann-Pick disease type C.
Article
Pharmacology & Pharmacy
Yusei Yamada, Yoichi Ishitsuka, Yuki Kondo, Shuichi Nakahara, Asami Nishiyama, Toru Takeo, Naomi Nakagata, Keiichi Motoyama, Taishi Higashi, Hidetoshi Arima, Shunsuke Kamei, Tsuyoshi Shuto, Hirofumi Kai, Yuji Hayashino, Masatake Sugita, Takeshi Kikuchi, Fumio Hirata, Toru Miwa, Hiroki Takeda, Yorihisa Orita, Takahiro Seki, Tomoko Ohta, Yuki Kurauchi, Hiroshi Katsuki, Muneaki Matsuo, Katsumi Higaki, Kousaku Ohno, Shirou Matsumoto, Takumi Era, Tetsumi Irie
Summary: The study showed that HP-gamma-CD forms a stable 1:1 inclusion complex with cholesterol, and has almost equivalent therapeutic effects in treating NPC compared to HP-beta-CD. HP-gamma-CD has lower toxicity than HP-beta-CD, and demonstrates the same efficacy in treating NPC models.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Denzil Furtado, Christina Cortez-Jugo, Ya Hui Hung, Ashley I. Bush, Frank Caruso
Summary: Researchers successfully used NPC1-encoded mRNA to combat protein insufficiency and pathogenic phenotype caused by biallelic NPC1 mutations, achieving treatment for the rare disease NP-C1. The gene engineering strategies greatly improved the expression efficiency of the mRNA.
MOLECULAR PHARMACEUTICS
(2022)
Article
Medicine, Research & Experimental
Yusei Yamada, Toru Miwa, Masaki Nakashima, Aina Shirakawa, Akira Ishii, Nanami Namba, Yuki Kondo, Toru Takeo, Naomi Nakagata, Keiichi Motoyama, Taishi Higashi, Hidetoshi Arima, Yuki Kurauchi, Takahiro Seki, Hiroshi Katsuki, Yasuyo Okada, Atsushi Ichikawa, Katsumi Higaki, Ken Hayashi, Kentaro Minami, Naoki Yoshikawa, Ryuji Ikeda, Yoshihide Ishikawa, Tomohito Kajii, Kyoko Tachii, Hiroki Takeda, Yorihisa Orita, Muneaki Matsuo, Tetsumi Irie, Yoichi Ishitsuka
Summary: By comparing the two cyclodextrins, researchers found that G2-gamma-CD showed lower ototoxicity in treating NPC and was considered a cholesterol solubilizer with physicochemical properties and biocompatibility suitable for clinical application.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Rita Pepponi, Roberta De Simone, Chiara De Nuccio, Sergio Visentin, Andrea Matteucci, Antonietta Bernardo, Patrizia Popoli, Antonella Ferrante
Summary: In this study, it was found that increasing adenosine levels may represent a new therapeutic approach for NPC. Experimental evidence from animal models and patient cells indicates that increasing adenosine levels by inhibiting the equilibrative nucleoside transporter (ENT1) can reduce lipid accumulation and improve mitochondrial deficits in NPC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Shaun C. Bolton, Vina Soran, Mercedes Pineda Marfa, Jackie Imrie, Paul Gissen, Helena Jahnova, Reena Sharma, Simon Jones, Saikat Santra, Ellen Crushell, Miriam Stampfer, Maria Jose Coll, Charlotte Dawson, Toni Mathieson, James Green, Andrea Dardis, Bruno Bembi, Marc C. Patterson, Marie T. Vanier, Tarekegn Geberhiwot
Summary: This study analyzed clinical features of 203 NPC patients from six European countries based on data from the International Niemann-Pick Disease Registry. The study found that the age distribution of the disease was relatively equal and neurological symptoms such as ataxia, dysphagia, and dysarthria were frequently observed in all age categories. The study also mentioned a composite disability scale used to evaluate the disability level of patients.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Ana C. Carreira, Sarka Pokorna, Ana E. Ventura, Mathew W. Walker, Anthony H. Futerman, Emyr Lloyd-Evans, Rodrigo F. M. de Almeida, Liana C. Silva
Summary: Niemann-Pick disease type C (NPC) is a complex and rare pathology primarily linked to mutations in the NPC1 gene. The abnormal accumulation of sphingosine may play a key role in the development of NPC, impacting membrane fluidity. Research shows that the addition of sphingosine can alter membrane fluidity, providing new insights into the pathophysiology of NPC.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Biochemistry & Molecular Biology
Nina H. Pipalia, Syed Z. Saad, Kanagaraj Subramanian, Abigail Cross, Aisha Al-Motawa, Kunal Garg, Brian S. J. Blagg, Len Neckers, Paul Helquist, Olaf Wiest, Daniel S. Ory, Frederick R. Maxfield
Summary: Inhibition of HSP90 clears cholesterol from LE/Ly in NPC1(I1061T) fibroblasts and enhances delivery of mutant NPC1(I1061T) protein. Additionally, HSP90 inhibition increases HSP70 expression, and overexpression of HSP70 reduces cholesterol storage in NPC1(I1061T) fibroblasts. This suggests that HSP90 inhibitors may improve NPC1 protein folding and relieve cholesterol accumulation in NPC1 mutant fibroblasts by increasing other chaperones.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Niamh X. Cawley, Anna T. Lyons, Daniel Abebe, Rachel Luke, Julia Yerger, Rebecca Telese, Christopher A. Wassif, Joan E. Bailey-Wilson, Forbes D. Porter
Summary: Complex asparagine-linked glycosylation plays a critical role in cellular functions. The deficiency of MGAT5, a key enzyme involved in this process, leads to increased severity of NPC1 disease in mice. The reduction in asparagine-linked glycosylation is associated with the progression of NPC1 disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Rania Hallaq, Floriana Volpicelli, Inmaculada Cuchillo-Ibanez, Claudie Hooper, Keiko Mizuno, Dafe Uwanogho, Mirsada Causevic, Ayodeji Asuni, Alvina To, Salvador Soriano, K. Peter Giese, Simon Lovestone, Richard Killick
CELLULAR SIGNALLING
(2015)
Article
Chemistry, Applied
Tanya L. Cupino, Billy A. Watson, Alan C. Cupino, Keiji Oda, Mark G. Ghamsary, Salvador Soriano, Wolff M. Kirsch
CARBOHYDRATE POLYMERS
(2018)
Review
Cell Biology
Michael A. Castello, Salvador Soriano
AGEING RESEARCH REVIEWS
(2014)
Article
Clinical Neurology
Michael A. Castello, John David Jeppson, Salvador Soriano
Article
Neurosciences
Tamara Blutstein, Michael A. Castello, Shaun S. Viechweg, Maria M. Hadjimarkou, Joseph A. McQuail, Mary Holder, Loren P. Thompson, Jessica A. Mong
NEUROTOXICITY RESEARCH
(2013)
Article
Multidisciplinary Sciences
Brendan Gongol, Traci L. Marin, John D. Jeppson, Karina Mayagoitia, Samuel Shin, Nicholas Sanchez, Wolff M. Kirsch, Harry V. Vinters, Christopher G. Wilson, Othman Ghribi, Salvador Soriano
SCIENTIFIC REPORTS
(2017)
Article
Neurosciences
Samuel D. Shin, Alexandra Shin, Karina Mayagoitia, Christopher G. Wilson, Denise L. Bellinger, Salvador Soriano
NEUROSCIENCE LETTERS
(2019)
Article
Immunology
Samuel D. Shin, Alexandra Shin, Karina Mayagoitia, Lorraine Siebold, Marsilio Rubini, Christopher G. Wilson, Denise L. Bellinger, Salvador Soriano
JOURNAL OF NEUROINFLAMMATION
(2019)
Article
Behavioral Sciences
Karina Mayagoitia, Sam D. Shin, Marsilio Rubini, Lorraine Siebold, Christopher G. Wilson, Denise L. Bellinger, Johnny D. Figueroa, Salvador Soriano
BEHAVIOURAL BRAIN RESEARCH
(2020)
Article
Neurosciences
Michael A. Castello, Joseph G. Gleeson
Summary: Cortical development involves various stages such as neurogenesis, migration, maturation, and myelination of immature neurons. Genetic mutations can result in malformations of cortical development, while mTOR inhibitors may have potential in treating treatment-resistant epilepsy.
CURRENT OPINION IN NEUROBIOLOGY
(2021)
Meeting Abstract
Pediatrics
Nicole E. Hickman, Maayan Yakir, Begem Lee, Michelle Sahagian, Michael A. Castello
Article
Pediatrics
Jenny K. Koo, Laurel Moyer, Michael A. Castello, Yassar Arain
PEDIATRIC QUALITY & SAFETY
(2020)