6533b85efe1ef96bd12c0851
RESEARCH PRODUCT
Expression of vesicle-associated membrane-protein-associated protein B cleavage products in peripheral blood leukocytes and cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis
Tiziana CollettiD. RussoP. GuarneriV. La BellaGiacoma GalizziIrene DeiddaRosa PassantinoCaterina Casciosubject
MalePathologymedicine.medical_specialtyamyotrophic lateral sclerosisnematode major sperm proteinproteolysisVesicular Transport ProteinsStatistics Nonparametriccerebrospinal fluidCerebrospinal fluidparasitic diseasesLeukocytesmedicineHumansperipheral blood leukocytesSecretionAmyotrophic lateral sclerosisAgedbiologybusiness.industryEndoplasmic reticulumvesicle-associated membrane-protein-associated protein AMiddle AgedVAPBmedicine.diseaseMolecular biologyvesicle-associated membrane-protein-associated protein Bamyotrophic lateral sclerosis cerebrospinal fluid nematode major sperm protein peripheral blood leukocytes proteolysis vesicleassociated membraneprotein- associated protein A vesicleassociated membraneprotein- associated protein BMolecular WeightBlotSettore BIO/12 - Biochimica Clinica E Biologia Molecolare ClinicaVesicle-associated membrane proteinNeurologyMutationbiology.proteinSettore MED/26 - NeurologiaFemaleNeurology (clinical)Antibodybusinessdescription
Background and purpose Vesicle-associated membrane-protein-associated protein B (VAPB) is an endoplasmic reticulum (ER) resident protein participating in ER function, vesicle trafficking, calcium homeostasis and lipid transport. Its N-terminal domain, named MSP, is cleaved and secreted, serving as an extracellular ligand. VAPB mutations are linked to autosomal-dominant motor neuron diseases, including amyotrophic lateral sclerosis (ALS) type 8. An altered VAPB function is also suspected in sporadic ALS (SALS). Methods The expression pattern of VAPB cleavage and secreted products in the peripheral blood leukocytes (PBL) and cerebrospinal fluid (CSF) of SALS patients and neurological controls was assessed. PBL from healthy controls were also analyzed. Assays were carried out through western blotting, using an anti-VAPB (N-terminal) antibody. Results Two VAPB fragments containing the MSP domain (17 kDa and 14 kDa molecular sizes) were identified in PBL of SALS and controls, with no significant differences amongst groups. In CSF, only the 14 kDa VAPB MSP fragment was expressed and a corresponding VAPA fragment was not detected. The CSF VAPB fragment was absent in 58.7% of SALS patients, of whom 79.2% were bulbar onset (P = 0.001, bulbar versus spinal). Conclusions The absence of the CSF VAPB MSP fragment from most bulbar-onset SALS patients suggests a specific alteration of brain-derived VAPB cleavage and secretion in this group of patients, and hints at a role of VAPB in the pathophysiology of this motor neuron disease.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-12-26 |