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Authors
Abstract(s)
A transtirretina (TTR) é uma proteína tetramérica, que está presente no plasma
e líquido cefalorraquidiano (LCR) de vertebrados.
As suas principais funções biológicas conhecidas englobam o transporte da
tiroxina (T4) e do retinol (vitamina A) através da formação de um complexo com a
proteína de ligação ao retinol (RBP). Adicionalmente, tem sido demonstrado que a
TTR é capaz de ligar e sequestrar o péptido beta amilóide (A-Beta), enfraquecendo a
sua deposição nos tecidos nervosos, uma característica chave da doença de
Alzheimer (AD). Assim, tem sido sugerido um papel protector desta proteína contra o
desenvolvimento da AD, suportado por estudos que indicam uma correlação negativa
entre os níveis da TTR no LCR e o grau de severidade desta doença
neurodegenerativa.
O fígado e os plexos coroideus do cérebro estão bem documentados como os
principais locais de síntese da TTR, mas recentemente têm surgido evidências que
apontam para a expressão desta proteína noutras regiões do cérebro, suscitando
alguma controvérsia.
Numa tentativa de contribuir para a resolução desta controvérsia foram
realizadas experiências de hibridação in situ (ISH) e imunohistoquímica (IHC) num
cérebro de ratinho wild-type previamente seriado, de forma a caracterizar a
distribuição celular da TTR neste órgão.
Os resultados obtidos indicam que para além de uma intensa marcação nas
células epiteliais do PC, como esperado, o mRNA da TTR está igualmente presente
em regiões específicas do parênquima cerebral, como o cerebelo e o bolbo
raquidiano, com possíveis implicações nas propriedades desta proteína no cérebro.
Transthyretin (TTR) is a tetrameric protein which exists in the serum and cerebrospinal fluid (CSF) of vertebrates. It’s main biological known functions comprise the transport of tyroxine (T4) and retinol (vitamin A) through the formation of a complex with the retinol binding protein (RBP). Additionally, it has been shown that TTR is capable to bind and sequester beta amyloid peptide (A-Beta), weakening it’s deposition in nervous tissues, a key feature of Alzheimer’s disease (AD). Consequently, it has been suggested a protective role for this protein against the development of AD, supported by reports that indicate a negative correlation between the levels of TTR in the CSF and the severity degree of this neurodegenerative disease. The liver and the brain choroid plexus (CP) are well documented as the major sites of TTR synthesis, however recently, evidence has emerged that aim to an expression of this protein in others regions of the brain, prompting some controversy. In an attempt to contribute to the resolution of this controversy, in situ hybridization (ISH) and imunohistochemical (IHC) investigations were performed in wild-type mice brain, previously serialized, in order to characterize the cellular distribution of TTR in this organ. The acquired data indicates that besides an intense staining in the PC epithelial cells, as expected, the mRNA of TTR is also present in specific regions of the cerebral parenchyma, such as the cerebellum and rachidian bulb, with possible implications on the properties of this protein in the brain.
Transthyretin (TTR) is a tetrameric protein which exists in the serum and cerebrospinal fluid (CSF) of vertebrates. It’s main biological known functions comprise the transport of tyroxine (T4) and retinol (vitamin A) through the formation of a complex with the retinol binding protein (RBP). Additionally, it has been shown that TTR is capable to bind and sequester beta amyloid peptide (A-Beta), weakening it’s deposition in nervous tissues, a key feature of Alzheimer’s disease (AD). Consequently, it has been suggested a protective role for this protein against the development of AD, supported by reports that indicate a negative correlation between the levels of TTR in the CSF and the severity degree of this neurodegenerative disease. The liver and the brain choroid plexus (CP) are well documented as the major sites of TTR synthesis, however recently, evidence has emerged that aim to an expression of this protein in others regions of the brain, prompting some controversy. In an attempt to contribute to the resolution of this controversy, in situ hybridization (ISH) and imunohistochemical (IHC) investigations were performed in wild-type mice brain, previously serialized, in order to characterize the cellular distribution of TTR in this organ. The acquired data indicates that besides an intense staining in the PC epithelial cells, as expected, the mRNA of TTR is also present in specific regions of the cerebral parenchyma, such as the cerebellum and rachidian bulb, with possible implications on the properties of this protein in the brain.
Description
Keywords
Transtirretina Doença de Alzheimer