Study of BDNF Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntington’s Disease

Study of BDNF Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntington’s Disease

Publication date: Jul 09, 2019

Huntington disease (HD, 1.3/10 000) is an autosomal dominant disease due to an abnormal expansion of CAG triplets in HTT gene. Several pathophysiological mechanisms have been evoked, including an alteration of the signaling pathway of the Brain Derived Neurotrophic Factor (BDNF), a neurotrophic factor involved in the survival of neurons (striatal and hippocampal) and synaptic plasticity. BDNF is synthesized at the level of cortical neurons and transported, through the axonal transport in which the Htt is involved, to the nerve endings; it’s then secreted in response to excitatory synaptic activity, especially at the level of glutamatergic synapses. Besides, at the postsynaptic level it binds with great specificity to TrkB receptors (tropomyosin-related kinase receptors B) with a neuroprotective effect on dendritic and axonal growth and an increase in synaptic plasticity, especially at the level of the striatum and the hippocampus (Benarroch 2015). BDNF is decreased in the brain of animal models, as well as in patients with HD; the alteration of this pathway would occur in the early stages of the disease (Chiara Zuccato and Cattaneo 2007) (Saudou and Humbert 2016) (Virlogeux et al. 2018). In the context of concomitant multiple treatments, the BNDF pathway may be one of the therapeutic targets of HD. Moreover, in HD it remains essential to detect biological markers representative of the different pathogenic pathways that can be tested in vivo in humans to confirm the hypotheses developed at the level of basic research; these biomarkers could subsequently become biomarkers of disease progression and/or biomarkers of therapeutic efficacy of potential targeted treatments. Therefore, this study aims to characterize potential biomarkers of the BNDF pathway in plasma and CSF in subjects with HD and to confirm the importance of this pathogenic mechanism in vivo in humans.

Concepts Keywords
Anamnestic Genotyping
Assay MRI
Autosomal Dominant Huntingtin
Axonal Growth Cerebrospinal fluid
Axonal Transport Biomarkers
BDNF Magnetic resonance imaging
Biobank Brain-derived neurotrophic factor
Biomarkers Developmental neuroscience
Blood Plasma Branches of biology
Blood Test
Bordeaux
Brain
Case Control Study
Central Nervous System
Cerebrospinal Fluid
Cognitive
Correlation
Cortical
Digit Span
Evolution
Excitatory
Exon
France
Functional MRI
Gene
Genotyping
Glutamatergic
Hippocampal
Hippocampus
Huntington
Informed Consent
Kinase
LCR
Lumbar Puncture
Montpellier
MRI
Multimodal
National Insurance
Nerve Endings
Neurodegenerative
Neurofilament
Neurons
Neuroprotective
Neuropsychological Tests
Neurotrophic Factor
NFL
Nimes
Pathogenic
Pathology
Pathophysiological
Plasma
Poitiers
Polymorphism
Postsynaptic
Receptors
Striatal
Striatum
Subgroup
Synapses
Synaptic
Synaptic Plasticity
Targeted Treatments
Tensor
Test
TrkB
Tropomyosin
Vivo

Semantics

Type Source Name
gene UNIPROT ALG3
gene UNIPROT NR4A2
disease MESH contraindications
gene UNIPROT CYREN
disease MESH diagnosis
gene UNIPROT LAMC2
gene UNIPROT CSF2
disease MESH disease progression
disease MESH multiple
disease MESH growth
gene UNIPROT NTRK2
gene UNIPROT RXFP2
gene UNIPROT SLC6A4
gene UNIPROT HTT
disease DOID autosomal dominant disease
disease DOID Huntington disease
disease MESH Huntington disease
gene UNIPROT BDNF

Original Article

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