A5048041840- Hereditary Neurological Disorders
- Neurological diseases and metabolism
- Muscle Physiology and Disorders
- Nerve injury and regeneration
- Genetic Neurodegenerative Diseases
- Botulinum Toxin and Related Neurological Disorders
- Nutrition and Health in Aging
- RNA regulation and disease
- Virus-based gene therapy research
- Microtubule and mitosis dynamics
- Porphyrin Metabolism and Disorders
- Adipose Tissue and Metabolism
- Vitamin C and Antioxidants Research
- Calpain Protease Function and Regulation
- Cancer-related molecular mechanisms research
- Plant Reproductive Biology
- Toxin Mechanisms and Immunotoxins
- Cancer Cells and Metastasis
- RNA Interference and Gene Delivery
- Cellular Mechanics and Interactions
- Metabolism, Diabetes, and Cancer
- Barrier Structure and Function Studies
- Connexins and lens biology
- Viral Infections and Immunology Research
- Neurogenetic and Muscular Disorders Research
Nationwide Children's Hospital
2019-2025
Boğaziçi University
2012-2018
University of Tübingen
2014
Hertie Institute for Clinical Brain Research
2014
Dr. John T. Macdonald Foundation
2014
University of Miami
2014
University of Duisburg-Essen
2014
Technical University of Munich
2014
Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES) of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ∼45% (17/37) families. Three candidate genes are proposed, supported by combination genetic vivo studies. Aggregate analysis mutation data revealed significantly increased number rare variants across...
To identify a novel disease gene in 2 families with autosomal recessive hereditary spastic paraplegia (HSP).We used whole-exome sequencing to the underlying genetic cause apparently paraplegia. Endogenous expression as well subcellular localization of wild-type and mutant protein were studied support pathogenicity identified mutations.In families, we compound heterozygous or homozygous mutations kinesin KIF1C type 58 (SPG58). SPG58 can be complicated by cervical dystonia cerebellar ataxia....
Sarcopenia is progressive loss of muscle mass and strength, occurring during normal aging with significant consequences on the quality life for elderly. Neurotrophin 3 (NT-3) an important autocrine factor supporting Schwann cell survival differentiation stimulating axon regeneration myelination. NT-3 involved in maintenance neuromuscular junction (NMJ) integrity, restoration impaired radial growth fibers through activation Akt/mTOR pathway. We tested efficacy gene transfer therapy wild type...
Multiple sclerosis (MS) is an immune-mediated chronic inflammatory and neurodegenerative disease of the central nervous system (CNS) affecting more than 2.5 million patients worldwide. Chronic demyelination in CNS has important role perpetuating axonal loss increases difficulty promoting remyelination. Therefore, regenerative, neuroprotective strategies are essential to overcome this impediment rescue integrity function. Neurotrophin 3 (NT-3) immunomodulatory anti-inflammatory properties,...
PLA2G6-associated neurodegeneration (PLAN) and hereditary spastic paraplegia (HSP) are 2 groups of heterogeneous neurodegenerative diseases. In this study, we report PLA2G6 gene mutations in 3 families from Turkey, Morocco, Romania. Two affected Turkish siblings presenting HSP adds the disease to PLAN phenotypes. They were homozygous for missense c.2239C>T, p.Arg747Trp variant ages onset 9 21. Parkinsonism, dystonia or cognitive decline not clinical elements these patients contrary cases...
Abstract X-linked Charcot-Marie-Tooth neuropathy (CMTX) is caused by mutations in the gene encoding Gap Junction Protein Beta-1 (GJB1)/Connexin32 (Cx32) Schwann cells. Neurotrophin-3 (NT-3) an important autocrine factor supporting cell survival and differentiation stimulating axon regeneration myelination. Improvements these parameters have been shown previously a CMT1 model, Trembler J mouse, with NT-3 transfer therapy. For this study, scAAV1.tMCK.NT-3 was delivered to gastrocnemius muscle...
// Neslihan Zohrap 1 , Özge Saatci 2 Burcak Ozes Ipek Coban 3 Hasan Murat Atay 4 Esra Battaloglu Özgür Şahin and Kuyas Bugra 1, 5 Department of Molecular Biology Genetics, Bogazici University, Istanbul, Turkey Bilkent Ankara, Pathology, Istanbul Florence-Nightingale Hospital, General Surgery, Gayrettepe Life Sciences Center, Correspondence to: Bugra, email: bugra@boun.edu.tr Keywords: SIK2; tumor suppressor; breast cancer; Ras/ERK PI3K/Akt signaling; EMT Received: October 19,...
Glycyl-tRNA synthetase mutations are associated to the Charcot-Marie-Tooth disease type-2D. The GarsP278KY/+ model for type-2D is known best its early onset severe neuropathic phenotype with findings including reduced axon size, slow conduction velocities and abnormal neuromuscular junction. Muscle involvement remains largely unexamined. We tested efficacy of neurotrophin 3 gene transfer therapy in two Gars mutants (GarsP278KY/+ ) milder (GarsΔETAQ/+ phenotypes via intramuscular injection...
Objectives:The aims of this study were to evaluate the sonographic findings patients with hereditary neuropathy liability pressure palsies (HNPP) and examine correlation between electrophysiological findings.Methods:Nine whose indicated HNPP diagnosis was confirmed by genetic analysis enrolled in study. The median, ulnar, peroneal, tibial nerves evaluated ultrasonography.Results:We ultrasonographically 18 nerves. Nerve enlargement identified peroneal at typical sites compression. None had...
Limb girdle muscular dystrophy (LGMD) 2A/R1, caused by mutations in the CAPN3 gene and loss of function, is known to play a role disease pathogenicity. In this study, AAVrh74.tMCK.CAPN3 was delivered systemically two different age groups knockout (KO) mice; each group included treatment cohorts receiving low (1.17 × 1014 vg/kg) high (2.35 doses vector untreated controls. Treatment efficacy tested 20 weeks after delivery using functional (treadmill), physiological (in vivo muscle...
Bilir B, Yapici Z, Yalcinkaya C, Baris I, Carvalho CMB, Bartnik M, Ozes Eraksoy Lupski JR, Battaloglu E. High frequency of GJA12 / GJC2 mutations in Turkish patients with Pelizaeus–Merzbacher disease. disease is an early onset dysmyelinating leukodystrophy. About 80% PMD cases have been associated duplications and the proteolipid protein 1 ( PLP1 ) gene. Pelizaeus–Merzbacher‐like a genetically heterogeneous autosomal recessive rarely caused by gap junction α 12 The molecular basis was...
Sarcopenia, an age-related loss of muscle mass, is a critical factor that affects the health older adults. The SOD1KO mouse deficient Cu/Zn superoxide dismutase, used as accelerated aging model. We previously showed NT-3 improves fibre size by activating mTOR pathway, suggesting potential for attenuating loss. This study assessed therapeutic efficacy AAV1.NT-3 in this model.Twelve 6 months old mice were injected intramuscularly with 1 × 1011 vg dose AAV1.tMCK.NT-3, and 13 age-matched...
Abstract Charcot–Marie–Tooth Type 4C (CMT4C) is associated with mutations in the SH3 domain and tetratricopeptide repeats 2 (SH3TC2) gene, primarily expressed Schwann cells (SCs). Neurotrophin-3 (NT-3) an important autocrine factor for SC survival differentiation, it stimulates neurite outgrowth myelination. In this study, scAAV1.tMCK.NT-3 was delivered intramuscularly to 4-week-old Sh3tc2−/− mice, a model CMT4C, treatment efficacy assessed at 6-month post-gene delivery. Efficient transgene...
Hücredeki proteinlerin toplamına proteom, proteomun hücre içindeki stabil durumuna proteostaz denilir.Proteostazın korunması için, doğru konsantrasyonu, hatasız ekspresyonu, düzgün üç-boyutlu katlanması, translokasyonu ve gerekli durumlarda yıkımı sağlanmalıdır.Genetik çevresel faktörler sonucu yanlış katlanma agregasyona-yatkın bir konformasyona dönüşmesi, stresini artırır