Journal of rare diseases research & treatment最新文献_第6页

Mechanism-based disease similarity. 基于机制的疾病相似性。

Journal of rare diseases research & treatment Pub Date : 2016-01-01 Epub Date: 2016-10-18 DOI: 10.29245/2572-9411/2016/3.1044

Mehdi B Hamaneh, Yi-Kuo Yu

引用次数: 0

Lenz-Majewski syndrome: How a single mutation leads to complex changes in lipid metabolism. Lenz-Majewski综合征:单一突变如何导致脂质代谢的复杂变化。

Journal of rare diseases research & treatment Pub Date : 2016-01-01 Epub Date: 2016-12-29 DOI: 10.29245/2572-9411/2017/1.1080

Mira Sohn, Tamas Balla

{"title":"Lenz-Majewski syndrome: How a single mutation leads to complex changes in lipid metabolism.","authors":"Mira Sohn, Tamas Balla","doi":"10.29245/2572-9411/2017/1.1080","DOIUrl":"https://doi.org/10.29245/2572-9411/2017/1.1080","url":null,"abstract":"Lenz-Majewski syndrome (LMS) is a rare disease presenting with complex physical and mental abnormalities. Whole exome sequencing performed on five LMS-affected individuals has identified gain-of-function mutations in the PTDSS1 gene encoding phosphatidylserine synthase 1 (PSS1) enzyme. These mutations all rendered PSS1 insensitive to PS-mediated product inhibition. In a recent study we showed that uncontrolled PS production by these mutant PSS1 enzymes lead to the accumulation of PS in the ER where it is not detected in normal cells. This increased PS in the ER in turn, activated the Sac1 phosphatase, which is responsible for the dephosphorylation of the minor lipid, phosphatidylinositol 4-phosphate (PI4P) in the ER. Increased Sac1 activity decreased PI4P levels both in the Golgi and the plasma membrane thereby dissipating the PI4P gradients set up by PI 4-kinase enzymes (PI4Ks) between these membranes and the ER. Such PI4P gradients at membrane contact sites have been shown to support the transports of structural lipids such as cholesterol and PS out of the ER by non-vesicular lipid transfer. Therefore, uncontrolled production of PS not only affects the PS status of cells but also initiates an avalanche of changes in the metabolism of other membrane lipids via affecting PI4P gradients throughout the cell. Recognition of the close metabolic interaction between PS synthesis and PI4P metabolism provided a new clue to better understand the molecular underpinning of this rare and severe disease.","PeriodicalId":91764,"journal":{"name":"Journal of rare diseases research & treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404757/pdf/nihms-1005985.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37041747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Rare disease models provide insight into inherited forms of neurodegeneration. 罕见疾病模型让我们深入了解神经变性的遗传形式。

Journal of rare diseases research & treatment Pub Date : 2016-01-01

Philippa C Fowler, Dwayne J Byrne, Niamh C O'Sullivan

{"title":"Rare disease models provide insight into inherited forms of neurodegeneration.","authors":"Philippa C Fowler, Dwayne J Byrne, Niamh C O'Sullivan","doi":"","DOIUrl":"","url":null,"abstract":"Hereditary spastic paraplegias (HSPs) are a group of inherited neurodegenerative conditions characterised by retrograde degeneration of the longest motor neurons in the corticospinal tract, resulting in muscle weakness and spasticity of the lower limbs. To date more than 70 genetic loci have been associated with HSP, however the majority of cases are caused by mutations that encode proteins responsible for generating and maintaining tubular endoplasmic reticulum (ER) structure. These ER-shaping proteins are vital for the long-term survival of axons, however the mechanisms by which mutations in these proteins give rise to HSP remain poorly understood. To begin to address this we have characterized in vivo loss of function models of two very rare forms of HSP caused by loss of the ER-shaping proteins ARL6IP1 (SPG61) and RTN2 (SPG12). These models display progressive locomotor defects, disrupted organisation of the tubular ER and length-dependant defects in the axonal mitochondrial network. Here we compare our findings with those associated with more common forms HSP including: Spastin, Atlastin-1 and REEP 1 which together account for over half of all cases of autosomal dominant HSP. Furthermore, we discuss recent observations in other HSP models which are directly implicated in mitochondrial function and localization. Overall, we highlight the common features of our rare models of HSP and other models of disease which could indicate shared mechanisms underpinning neurodegeneration in these disorders.","PeriodicalId":91764,"journal":{"name":"Journal of rare diseases research & treatment","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35080510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rationally combining anti-VEGF therapy with radiation in NF2 schwannoma. 将抗血管内皮生长因子疗法与放射治疗合理地结合用于 NF2 裂血管瘤。

Journal of rare diseases research & treatment Pub Date : 2016-01-01

Na Zhang, Xing Gao, Yingchao Zhao, Meenal Datta, Pinan Liu, Lei Xu

引用次数: 0

Mini-review on "A novel one-step purification of mouse factor IX". “一种新的一步法纯化小鼠因子IX”综述。

Journal of rare diseases research & treatment Pub Date : 2016-01-01 DOI: 10.29245/2572-9411/2016/2.1031

Sumita Choudhury, William E Plautz, Cosette Zacarias, Rinku Majumder

引用次数: 0