scholarly journals Evaluation of the Therapeutic Potential of Resveratrol-Loaded Nanostructured Lipid Carriers on Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay Patient-Derived Fibroblasts

2021 ◽  
pp. 110012
Author(s):  
Özlem Şen ◽  
Melis Emanet ◽  
Attilio Marino ◽  
Melike Belenli Gümüş ◽  
Martina Bartolucci ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Therapeutic Potential ◽  
Nanostructured Lipid Carriers ◽  
Spastic Ataxia

scholarly journals Development of Nanostructured Lipid Carriers for the Delivery of Idebenone in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

ACS Omega ◽  
2020 ◽  
Vol 5 (21) ◽  
pp. 12451-12466 ◽  
Author(s):  
Chiara Martinelli ◽  
Matteo Battaglini ◽  
Carlotta Pucci ◽  
Sara Gioi ◽  
Chiara Caracci ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Nanostructured Lipid Carriers ◽  
Spastic Ataxia

scholarly journals Novel compound heterozygous mutation in SACS gene leads to a milder autosomal recessive spastic ataxia of Charlevoix‐Saguenay, ARSACS , in a Finnish family

2016 ◽  
Vol 4 (12) ◽  
pp. 1151-1156 ◽  
Author(s):  
Johanna Palmio ◽  
Mikko Kärppä ◽  
Peter Baumann ◽  
Sini Penttilä ◽  
Jukka Moilanen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Spastic Ataxia

scholarly journals Biochemical Characterization of the GBA2 c.1780G>C Missense Mutation in Lymphoblastoid Cells from Patients with Spastic Ataxia

2018 ◽  
Vol 19 (10) ◽  
pp. 3099 ◽  
Author(s):  
Anna Malekkou ◽  
Maura Samarani ◽  
Anthi Drousiotou ◽  
Christina Votsi ◽  
Sandro Sonnino ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Autosomal Recessive ◽  
Biochemical Characterization ◽  
Fold Increase ◽  
Loss Of Function ◽  
Spastic Paraplegia ◽  
Spastic Ataxia ◽  
Autosomal Recessive Cerebellar Ataxia ◽  
Compensatory Effect

The GBA2 gene encodes the non-lysosomal glucosylceramidase (NLGase), an enzyme that catalyzes the conversion of glucosylceramide (GlcCer) to ceramide and glucose. Mutations in GBA2 have been associated with the development of neurological disorders such as autosomal recessive cerebellar ataxia, hereditary spastic paraplegia, and Marinesco-Sjogren-Like Syndrome. Our group has previously identified the GBA2 c.1780G>C [p.Asp594His] missense mutation, in a Cypriot consanguineous family with spastic ataxia. In this study, we carried out a biochemical characterization of lymphoblastoid cell lines (LCLs) derived from three patients of this family. We found that the mutation strongly reduce NLGase activity both intracellularly and at the plasma membrane level. Additionally, we observed a two-fold increase of GlcCer content in LCLs derived from patients compared to controls, with the C16 lipid being the most abundant GlcCer species. Moreover, we showed that there is an apparent compensatory effect between NLGase and the lysosomal glucosylceramidase (GCase), since we found that the activity of GCase was three-fold higher in LCLs derived from patients compared to controls. We conclude that the c.1780G>C mutation results in NLGase loss of function with abolishment of the enzymatic activity and accumulation of GlcCer accompanied by a compensatory increase in GCase.

scholarly journals Genetics of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Role of Sacsin in Neurodegeneration

2022 ◽  
Vol 23 (1) ◽  
pp. 552
Author(s):  
Jaya Bagaria ◽  
Eva Bagyinszky ◽  
Seong Soo A. An
Keyword(s):  
Neurodegenerative Diseases ◽  
Autosomal Recessive ◽  
Genetic Mutations ◽  
Compound Heterozygous ◽  
French Canadians ◽  
Pes Cavus ◽  
Spastic Ataxia ◽  
Mitochondrial Functions ◽  
Limb Deformities

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that was originally discovered in the population from the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region in Quebec. Although the disease progression of ARSACS may start in early childhood, cases with later onset have also been observed. Spasticity and ataxia could be common phenotypes, and retinal optic nerve hypermyelination is detected in the majority of patients. Other symptoms, such as pes cavus, ataxia and limb deformities, are also frequently observed in affected individuals. More than 200 mutations have been discovered in the SACS gene around the world. Besides French Canadians, SACS genetics have been extensively studied in Tunisia or Japan. Recently, emerging studies discovered SACS mutations in several other countries. SACS mutations could be associated with pathogenicity either in the homozygous or compound heterozygous stages. Sacsin has been confirmed to be involved in chaperon activities, controlling the microtubule balance or cell migration. Additionally, sacsin may also play a crucial role in regulating the mitochondrial functions. Through these mechanisms, it may share common mechanisms with other neurodegenerative diseases. Further studies are needed to define the exact functions of sacsin. This review introduces the genetic mutations discovered in the SACS gene and discusses its pathomechanisms and its possible involvement in other neurodegenerative diseases.

scholarly journals Therapeutic Potential of α-Synuclein Evolvability for Autosomal Recessive Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jianshe Wei ◽  
Gilbert Ho ◽  
Yoshiki Takamatsu ◽  
Eliezer Masliah ◽  
Makoto Hashimoto
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Therapeutic Potential ◽  
Gene Mutations ◽  
Mitochondrial Alteration ◽  
Rational Therapy ◽  
Ubiquitin Proteasome ◽  
Dominant Genes

The majority of Parkinson’s disease (PD) is sporadic in elderly and is characterized by α-synuclein (αS) aggregation and other alterations involving mitochondria, ubiquitin-proteasome, and autophagy. The remaining are familial PD associated with gene mutations of either autosomal dominant or recessive inheritances. However, the former ones are similar to sporadic PD, and the latter ones are accompanied by impaired mitophagy during the reproductive stage. Since no radical therapies are available for PD, the objective of this paper is to discuss a mechanistic role for amyloidogenic evolvability, a putative physiological function of αS, among PD subtypes, and the potential relevance to therapy. Presumably, αS evolvability might benefit familial PD due to autosomal dominant genes and also sporadic PD during reproduction, which may manifest as neurodegenerative diseases through antagonistic pleiotropy mechanism in aging. Indeed, there are some reports describing that αS prevents apoptosis and mitochondrial alteration under the oxidative stress conditions, notwithstanding myriads of papers on the neuropathology of αS. Importantly, β-synuclein (βS), the nonamyloidogenic homologue of αS, might buffer against evolvability of αS protofibrils associated with neurotoxicity. Finally, it is intriguing to predict that increased αS evolvability through suppression of βS expression might protect against autosomal recessive PD. Collectively, further studies are warranted to better understand αS evolvability in PD pathogenesis, leading to rational therapy development.

scholarly journals Autosomal recessive spastic ataxia of charlevoix-saguenay (ARSACS): Case report of a novel nonsense mutation in the SACS gene

2020 ◽  
Vol 0 (0) ◽  
pp. 0
Author(s):  
Abdul Qavi ◽  
Ayush Agarwal ◽  
Divyani Garg ◽  
Akash Kharat
Keyword(s):  
Case Report ◽  
Nonsense Mutation ◽  
Autosomal Recessive ◽  
Spastic Ataxia

scholarly journals Assessment of the impact of an exercise program on the physical and functional capacity in patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay: An exploratory study

2018 ◽  
Vol 7 (3) ◽  
pp. 164-171 ◽  
Author(s):  
Olivier Audet ◽  
Hung Tien Bui ◽  
Maxime Allisse ◽  
Alain-Steve Comtois ◽  
Mario Leone
Keyword(s):  
Functional Capacity ◽  
Exploratory Study ◽  
Autosomal Recessive ◽  
Exercise Program ◽  
Spastic Ataxia ◽  
The Impact

Redox resetting of cisplatin-resistant ovarian cancer cells by cisplatin-encapsulated nanostructured lipid carriers

Nanomedicine ◽  
2021 ◽  
Author(s):  
Disha Mittal ◽  
Largee Biswas ◽  
Anita Kamra Verma
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Therapeutic Potential ◽  
Nanostructured Lipid Carriers ◽  
Ovarian Cancer Cells ◽  
Oxygen Species ◽  
X Ray Diffraction ◽  
X Ray ◽  
Resistance Markers ◽  
Fourier Transform Ir

Aim: To sensitize cisplatin (Cis)-resistant ovarian cancer cells toward Cis using Cis-loaded nanostructured lipid carriers (CisNLCs). Materials & methods: CisNLCs were synthesized and characterized using dynamic light scattering, Fourier transform IR and x-ray diffraction (XRD). Sensitivity of PA-1 and CaOV3 cells to Cis and its biotoxicity were assessed. Further, expression of the Cis-resistance markers GSTPi and  ATP7B, and apoptotic markers Bax, Bcl2 and Cas9 were quantified by real-time PCR. Results: The size of synthesized CisNLCs was approximately 179.3 ± 2.32 nm and surface charge was -33.9 ± 1.47 mV. IC50 was 210 μg/ml in PA-1 and 500 μg/ml in CaOV3. CisNLCs modulated reactive oxygen species levels in CaOV3 cells. Reduced GSTPi and decreased Cis efflux via ATP7B sequestration caused Cis to accumulate in cytoplasm, thereby augmenting apoptosis in cells. Conclusion: CisNLCs sensitize CaOV3 by redox resetting, indicating their immense therapeutic potential.

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