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The Diversity of Mechanisms Influenced by Transthyretin in Neurobiology: Development, Disease and Endocrine Disruption
- Source :
- Journal of Neuroendocrinology. 27:303-323
- Publication Year :
- 2015
- Publisher :
- Wiley, 2015.
-
Abstract
- Transthyretin (TTR) is a protein that binds and distributes thyroid hormones (THs). TTR synthesised in the liver is secreted into the bloodstream and distributes THs around the body, whereas TTR synthesised in the choroid plexus is involved in movement of thyroxine from the blood into the cerebrospinal fluid and the distribution of THs in the brain. This is important because an adequate amount of TH is required for normal development of the brain. Nevertheless, there has been heated debate on the role of TTR synthesised by the choroid plexus during the past 20 years. We present both sides of the debate and how they can be reconciled by the discovery of TH transporters. New roles for TTR have been suggested, including the promotion of neuroregeneration, protection against neurodegeneration, and involvement in schizophrenia, behaviour, memory and learning. Recently, TTR synthesis was revealed in neurones and peripheral Schwann cells. Thus, the synthesis of TTR in the central nervous system (CNS) is more extensive than previously considered and bolsters the hypothesis that TTR may play wide roles in neurobiological function. Given the high conservation of TTR structure, function and tissue specificity and timing of gene expression, this implies that TTR has a fundamental role, during development and in the adult, across vertebrates. An alarming number of 'unnatural' chemicals can bind to TTR, thus potentially interfering with its functions in the brain. One role of TTR is delivery of THs throughout the CNS. Reduced TH availability during brain development results in a reduced IQ. The combination of the newly discovered sites of TTR synthesis in the CNS, the increasing number of neurological diseases being associated with TTR, the newly discovered functions of TTR and the awareness of the chemicals that can interfere with TTR biology render this a timely review on TTR in neurobiology.
- Subjects :
- Central Nervous System
Thyroid Hormones
endocrine system
medicine.medical_specialty
Amyloid
Endocrinology, Diabetes and Metabolism
Central nervous system
Endocrine Disruptors
Cellular and Molecular Neuroscience
Cognition
Endocrinology
Cerebrospinal fluid
Central Nervous System Diseases
Internal medicine
medicine
Animals
Humans
Prealbumin
Neurons
biology
Endocrine and Autonomic Systems
Neurodegeneration
Brain
nutritional and metabolic diseases
Transporter
DNA
medicine.disease
Neuroregeneration
Retinol-Binding Proteins
Transthyretin
medicine.anatomical_structure
Choroid Plexus
Vertebrates
biology.protein
Choroid plexus
Schwann Cells
Neuroscience
Subjects
Details
- ISSN :
- 09538194
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroendocrinology
- Accession number :
- edsair.doi.dedup.....e183ef74e22e0079819ffabcb037b12d