keyword
https://read.qxmd.com/read/38348168/editorial-genetic-research-into-neurodegenerative-disorders
#21
EDITORIAL
Xiaoting Zheng, Jianhai Chen, Chunyu Li
No abstract text is available yet for this article.
2024: Frontiers in Neurology
https://read.qxmd.com/read/38345566/defining-the-progeria-phenome
#22
JOURNAL ARTICLE
Cecilie Worm, Maya Elena Ramirez Schambye, Garik V Mkrtchyan, Alexander Veviorskiy, Anastasia Shneyderman, Ivan V Ozerov, Alex Zhavoronkov, Daniela Bakula, Morten Scheibye-Knudsen
Progeroid disorders are a heterogenous group of rare and complex hereditary syndromes presenting with pleiotropic phenotypes associated with normal aging. Due to the large variation in clinical presentation the diseases pose a diagnostic challenge for clinicians which consequently restricts medical research. To accommodate the challenge, we compiled a list of known progeroid syndromes and calculated the mean prevalence of their associated phenotypes, defining what we term the 'progeria phenome'. The data were used to train a support vector machine that is available at https://www...
February 9, 2024: Aging
https://read.qxmd.com/read/38344647/postpartum-hypocupric-myelopathy-masquerading-as-acute-transverse-myelitis-a-case-report-and-literature-review-of-a-rare-presentation
#23
Nikhil Pantbalekundri, Sunil Kumar, Sourya Acharya, Gautam Bedi
The symptoms of transverse myelitis, an acute demyelinating inflammatory condition of the spinal cord, include motor, sensory, and bowel-bladder dysfunction that can develop suddenly or gradually. Several etiologies, such as bacterial, fungal, or viral infections, cancer, autoimmune diseases, vascular problems, and environmental variables, can cause it. The identification of copper deficiency myelopathy (CDM) as a curable cause of non-compressive inflammatory myelopathy has only occurred recently...
January 2024: Curēus
https://read.qxmd.com/read/38332048/ddhd2-whose-mutations-cause-spastic-paraplegia-type-54-enhances-lipophagy-via-engaging-atg8-family-proteins
#24
JOURNAL ARTICLE
Fei Jia, Xiaoman Wang, Yuhua Fu, Shi-Min Zhao, Boxun Lu, Chenji Wang
Hereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative disorders characterized by progressive lower limb spasticity and weakness. One subtype of HSP, known as SPG54, is caused by biallelic mutations in the DDHD2 gene. The primary pathological feature observed in patients with SPG54 is the massive accumulation of lipid droplets (LDs) in the brain. However, the precise mechanisms and roles of DDHD2 in regulating lipid homeostasis are not yet fully understood. Through Affinity Purification-Mass Spectroscopy (AP-MS) analysis, we identify that DDHD2 interacts with multiple members of the ATG8 family proteins (LC3, GABARAPs), which play crucial roles in lipophagy...
February 8, 2024: Cell Death and Differentiation
https://read.qxmd.com/read/38330475/genetic-myelopathies
#25
REVIEW
Kara Stavros
OBJECTIVE: This article provides an overview of genetic myelopathies, a diverse group of inherited, degenerative conditions that may be broadly categorized as motor neuron disorders, disorders of spinocerebellar degeneration, leukodystrophies, and hereditary spastic paraplegia. Clinical examples from each category are provided to illustrate the spectrum of genetic myelopathies and their distinguishing features that aid in differentiating genetic myelopathies from potentially treatable acquired causes of myelopathy...
February 1, 2024: Continuum: Lifelong Learning in Neurology
https://read.qxmd.com/read/38316990/the-ddhd2-stxbp1-interaction-mediates-long-term-memory-via-generation-of-saturated-free-fatty-acids
#26
JOURNAL ARTICLE
Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier
The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain...
February 5, 2024: EMBO Journal
https://read.qxmd.com/read/38306901/a-novel-homozygous-deletion-including-exon-1-of-fa2h-gene-causes-spastic-paraplegia-35-genetic-and-lipidomics-analysis-of-the-patients
#27
JOURNAL ARTICLE
Lidangzhi Mo, Xiaoling Tie, Fengyu Che, Liyu Zhang, Benchang Li, Guoxia Wang, Ying Yang
BACKGROUND: Fatty acid 2-hydroxylase (FA2H) is encoded by the FA2H gene, with mutations therein leading to the neurodegenerative condition, spastic paraplegia-35 (SPG35). We aim to elucidate the genetic underpinnings of a nonconsanguineous Chinese family diagnosed with SPG35 by examining the clinical manifestations, scrutinizing genetic variants, and establishing the role of FA2H mutation in lipid metabolism. METHODS: Using next-generation sequencing analysis to identify the pathogenic gene in this pedigree and family cosegregation verification...
March 2024: Pediatric Neurology
https://read.qxmd.com/read/38305941/neuroinflammatory-disease-signatures-in-spg11-related-hereditary-spastic-paraplegia-patients
#28
JOURNAL ARTICLE
Laura Krumm, Tatyana Pozner, Naime Zagha, Roland Coras, Philipp Arnold, Thanos Tsaktanis, Kathryn Scherpelz, Marie Y Davis, Johanna Kaindl, Iris Stolzer, Patrick Süß, Mukhran Khundadze, Christian A Hübner, Markus J Riemenschneider, Jonathan Baets, Claudia Günther, Suman Jayadev, Veit Rothhammer, Florian Krach, Jürgen Winkler, Beate Winner, Martin Regensburger
Biallelic loss of SPG11 function constitutes the most frequent cause of complicated autosomal recessive hereditary spastic paraplegia (HSP) with thin corpus callosum, resulting in progressive multisystem neurodegeneration. While the impact of neuroinflammation is an emerging and potentially treatable aspect in neurodegenerative diseases and leukodystrophies, the role of immune cells in SPG11-HSP patients is unknown. Here, we performed a comprehensive immunological characterization of SPG11-HSP, including examination of three human postmortem brain donations, immunophenotyping of patients' peripheral blood cells and patient-specific induced pluripotent stem cell-derived microglia-like cells (iMGL)...
February 2, 2024: Acta Neuropathologica
https://read.qxmd.com/read/38301322/a-retrospective-review-of-18-patients-with-childhood-onset-hereditary-spastic-paraplegia-nine-with-novel-variants
#29
REVIEW
Mehmet Akif Kilic, Edibe Pembegul Yildiz, Adnan Deniz, Orhan Coskun, Fulya Kurekci, Ridvan Avci, Hulya Maras Genc, Gozde Yesil, Sinan Akbas, Ahmet Yesilyurt, Bulent Kara
BACKGROUND: Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative disorders. Our objective was to determine the clinical and molecular characteristics of patients with genetically confirmed childhood-onset HSPs and to expand the genetic spectrum for some rare subtypes of HSP. METHODS: We reviewed the charts of subjects with genetically confirmed childhood-onset HSP. The age at the disease onset was defined as the point at which the delayed motor milestones were observed...
March 2024: Pediatric Neurology
https://read.qxmd.com/read/38292290/behr-s-syndrome-mimicking-a-case-of-hereditary-spastic-paraparesis
#30
JOURNAL ARTICLE
Rajesh Verma, Rajarshi Chakraborty
No abstract text is available yet for this article.
March 2024: ENeurologicalSci
https://read.qxmd.com/read/38291924/clinical-and-genetic-spectrum-in-a-large-cohort-of-hereditary-spastic-paraplegia
#31
JOURNAL ARTICLE
Yuwen Cao, Haoran Zheng, Zeyu Zhu, Li Yao, Wotu Tian, Li Cao
BACKGROUND: Next-generation sequencing-based molecular assessment has benefited the diagnosis of hereditary spastic paraplegia (HSP) subtypes. However, the clinical and genetic spectrum of HSP due to large fragment deletions/duplications has yet to be fully defined. OBJECTIVE: We aim to better characterize the clinical phenotypes and genetic features of HSP and to provide new thoughts on diagnosis. METHODS: Whole-exome sequencing (WES) was performed in patients with clinically suspected HSP, followed by multiple ligation-dependent probe amplification (MLPA) sequentially carried out for those with negative findings in known causative genes...
January 31, 2024: Movement Disorders: Official Journal of the Movement Disorder Society
https://read.qxmd.com/read/38286980/a-novel-homozygous-hpdl-variant-in-japanese-siblings-with-autosomal-recessive-hereditary-spastic-paraplegia-case-report-and-literature-review
#32
JOURNAL ARTICLE
Fumikazu Kojima, Yuji Okamoto, Masahiro Ando, Yujiro Higuchi, Takahiro Hobara, Junhui Yuan, Akiko Yoshimura, Akihiro Hashiguchi, Eiji Matsuura, Hiroshi Takashima
Biallelic variants of 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene have been linked to neurodegenerative disorders ranging from severe neonatal encephalopathy to early-onset spastic paraplegia. We identified a novel homozygous variant, c.340G > T (p.Gly114Cys), in the HPDL gene in two siblings with autosomal recessive hereditary spastic paraplegia (HSP). Despite sharing the same likely pathogenic variant, the older sister had pure HSP, whereas her brother had severe and complicated HSP, accompanied by early-onset mental retardation and abnormalities in magnetic resonance imaging...
January 29, 2024: Neurogenetics
https://read.qxmd.com/read/38281682/the-reelin-receptor-apoer2-is-a-cargo-for-the-adaptor-protein-complex-ap-4-implications-for-hereditary-spastic-paraplegia
#33
JOURNAL ARTICLE
Mario O Caracci, Héctor Pizarro, Carlos Alarcón-Godoy, Luz M Fuentealba, Pamela Farfán, Raffaella De Pace, Natacha Santibañez, Viviana A Cavieres, Tammy P Pástor, Juan S Bonifacino, Gonzalo A Mardones, María-Paz Marzolo
Adaptor protein complex 4 (AP-4) is a heterotetrameric complex that promotes export of selected cargo proteins from the trans-Golgi network. Mutations in each of the AP-4 subunits cause a complicated form of Hereditary Spastic Paraplegia (HSP). Herein, we report that ApoER2, a receptor in the Reelin signaling pathway, is a cargo of the AP-4 complex. We identify the motif ISSF/Y within the ApoER2 cytosolic domain as necessary for interaction with the canonical signal-binding pocket of the µ4 (AP4M1) subunit of AP-4...
January 26, 2024: Progress in Neurobiology
https://read.qxmd.com/read/38277988/pcyt2-deficiency-in-saarlooswolfdogs-with-progressive-retinal-central-and-peripheral-neurodegeneration
#34
JOURNAL ARTICLE
Matthias Christen, Anna Oevermann, Stefan Rupp, Frédéric M Vaz, Eric J M Wever, Barbara K Braus, Vidhya Jagannathan, Alexandra Kehl, Marjo K Hytönen, Hannes Lohi, Tosso Leeb
We investigated a syndromic disease comprising blindness and neurodegeneration in 11 Saarlooswolfdogs. Clinical signs involved early adult onset retinal degeneration and adult-onset neurological deficits including gait abnormalities, hind limb weakness, tremors, ataxia, cognitive decline and behavioral changes such as aggression towards the owner. Histopathology in one affected dog demonstrated cataract, retinal degeneration, central and peripheral axonal degeneration, and severe astroglial hypertrophy and hyperplasia in the central nervous system...
January 21, 2024: Molecular Genetics and Metabolism
https://read.qxmd.com/read/38276084/primary-lateral-sclerosis-an-overview
#35
REVIEW
Veria Vacchiano, Luigi Bonan, Rocco Liguori, Giovanni Rizzo
Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder which causes the selective deterioration of the upper motor neurons (UMNs), sparing the lower motor neuron (LMN) system. The clinical course is defined by a progressive motor disability due to muscle spasticity which typically involves lower extremities and bulbar muscles. Although classically considered a sporadic disease, some familiar cases and possible causative genes have been reported. Despite it having been recognized as a rare but distinct entity, whether it actually represents an extreme end of the motor neuron diseases continuum is still an open issue...
January 19, 2024: Journal of Clinical Medicine
https://read.qxmd.com/read/38275596/novel-homozygous-fa2h-variant-causing-the-full-spectrum-of-fatty-acid-hydroxylase-associated-neurodegeneration-spg35
#36
Alexander German, Jelena Jukic, Andreas Laner, Philipp Arnold, Eileen Socher, Angelika Mennecke, Manuel A Schmidt, Jürgen Winkler, Angela Abicht, Martin Regensburger
Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in FA2H and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, we present the prototypical workup of a novel FA2H variant, including clinical and in silico validation. An 18-year-old male patient presented with a history of childhood-onset progressive cognitive impairment, as well as progressive gait disturbance and lower extremity muscle cramps from the age of 15...
December 20, 2023: Genes
https://read.qxmd.com/read/38267061/treatment-of-zc4h2-variant-associated-spastic-paraplegia-with-selective-dorsal-rhizotomy-and-intensive-postoperative-rehabilitation-a-case-report
#37
JOURNAL ARTICLE
Toshiki Inotani, Akira Horaguchi, Yuko Morishita, Ayuko Yoshida, Misaki Otomo, Makoto Suzuki, Takehiko Inui, Yukimune Okubo, Shigemasa Komatsu, Chika Mizuno, Yuko Takahashi, Tatsuhiro Ochiai, Takeshi Kinjo, Takashi Asato, Jun Takayama, Gen Tamiya, Naoya Saijo, Atsuo Kikuchi, Kazuhiro Haginoya
No abstract text is available yet for this article.
January 25, 2024: Tohoku Journal of Experimental Medicine
https://read.qxmd.com/read/38252374/a-novel-atp13a2-variant-causing-complicated-hereditary-spastic-paraplegia
#38
JOURNAL ARTICLE
Fan Zhang, Peng Liu, Jiaxiang Li, Zhidong Cen, Wei Luo
BACKGROUND: ATP13A2 is a monogenic causative gene of Parkinson's disease, whose biallelic mutations can result in Kufor-Rakeb syndrome. Biallelic mutations in ATP13A2 have also been reported in pure or complicated hereditary spastic paraplegia (HSP). Here, we report clinical, neuroimaging, and genetic findings from a patient with a novel homozygous mutation in ATP13A2 presenting with HSP plus parkinsonism. METHODS: Whole genome sequencing was performed on the patient, a 46-year-old Chinese woman from a consanguineous family, to identify the genetic cause...
January 22, 2024: Neurological Sciences
https://read.qxmd.com/read/38242023/a-retrospective-cross-sectional-analysis-of-motor-development-cognition-and-mood-in-87-patients-with-childhood-onset-hereditary-spastic-paraplegias
#39
JOURNAL ARTICLE
Brooke M Marvel, Linsley Smith, Jonathan J Rios, Michelle R Christie
BACKGROUND: HSP is a heterogeneous group of rare genetic diseases. In childhood, little is known of the development and psychological manifestations. METHODS: Retrospective analysis of 87 patients with childhood-onset HSP. Patient consent was obtained and data regarding gross motor, fine motor, and language development; equipment usage; surgical procedures; cognition; and mood were collected at each clinic visit and by phone call and analyzed using mean, median, range, and interquartile ranges (IQRs)...
March 2024: Pediatric Neurology
https://read.qxmd.com/read/38233389/high-content-screening-identifies-a-small-molecule-that-restores-ap-4-dependent-protein-trafficking-in-neuronal-models-of-ap-4-associated-hereditary-spastic-paraplegia
#40
JOURNAL ARTICLE
Afshin Saffari, Barbara Brechmann, Cedric Böger, Wardiya Afshar Saber, Hellen Jumo, Dosh Whye, Delaney Wood, Lara Wahlster, Julian E Alecu, Marvin Ziegler, Marlene Scheffold, Kellen Winden, Jed Hubbs, Elizabeth D Buttermore, Lee Barrett, Georg H H Borner, Alexandra K Davies, Darius Ebrahimi-Fakhari, Mustafa Sahin
Unbiased phenotypic screens in patient-relevant disease models offer the potential to detect therapeutic targets for rare diseases. In this study, we developed a high-throughput screening assay to identify molecules that correct aberrant protein trafficking in adapter protein complex 4 (AP-4) deficiency, a rare but prototypical form of childhood-onset hereditary spastic paraplegia characterized by mislocalization of the autophagy protein ATG9A. Using high-content microscopy and an automated image analysis pipeline, we screened a diversity library of 28,864 small molecules and identified a lead compound, BCH-HSP-C01, that restored ATG9A pathology in multiple disease models, including patient-derived fibroblasts and induced pluripotent stem cell-derived neurons...
January 17, 2024: Nature Communications
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