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Potencialidades terapĂȘuticas das microvesĂculas
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Advisor(s)
Abstract(s)
As microvesĂculas sĂŁo um grupo heterogĂ©neo de vesĂculas esfĂ©ricas com um diĂąmetro de 100-1000 nm, formadas por brotamento/gemulação da membrana plasmĂĄtica da cĂ©lula. Os exossomas sĂŁo estruturas mais homogĂ©neas e mais pequenas (40-120 nm) do que as microvesĂculas. Ao contrĂĄrio das microvesĂculas, que sĂŁo abundantes na circulação sanguĂnea e derivam, essencialmente, de plaquetas, os exossomas sĂŁo derivados do compartimento endo-lisossomal. Estas estruturas tĂȘm sido detetadas no sangue e em vĂĄrios fluĂdos corporais (urina, secreçÔes broncoalveolar, muco, saliva, bĂlis, ascite, fluido cĂ©rebroespinhal e leite materno). A sua composição Ă© heterogĂ©nea e depende do tipo de cĂ©lula de origem. A composição diferenciada Ă© um prĂ©-requisito para a sua função potencial de biomarcador patofisiolĂłgico. De facto, a sua constituição especĂfica em proteĂnas transmembranares, proteĂnas solĂșveis, mRNA e microRNA pode ser representativa de uma condição fisiolĂłgica normal ou patolĂłgica. Deste modo, um passo crĂtico para a utilização, no futuro, de microvesĂculas e endossomas como biomarcadores consistirĂĄ na identificação de correlaçÔes inequĂvocas entre os diferentes estados de progressĂŁo da doença e o respetivo padrĂŁo bioquĂmico. Adicionalmente, a sua deteção e caracterização de forma rĂĄpida, usando biossensores baseados em nanopartĂculas, deverĂĄ permitir a sua utilização como biomarcadores de doenças de etiologia muito diversa, tais como tais como o cancro, doenças metabĂłlicas e doenças neurodegenerativas na prĂĄtica clĂnica. Para alĂ©m do seu papel no domĂnio da prevenção, diagnĂłstico e monitorização da progressĂŁo da doença, tambĂ©m poderĂŁo desempenhar, no futuro, uma papel importante ao nĂvel da terapia e da avaliação do sucesso terapĂȘutico das doenças em que se encontrarem patofisologicamente implicados.
The microvesicles are a heterogeneous group of spherical vesicles with a diameter of 100-1000 nm formed by budding of the plasma membrane of the cell. The exosomes are more homogeneous and smaller (40-120 nm) structures than the microvesicles. Unlike microvesicles, which are abundant in the blood circulation and derived primarily from platelets, exosomes are originated in the endolysosomal cell compartment. These structures have been detected in the blood and in various body fluids (urine, bronchoalveolar secretions, mucus, saliva, bile, ascyte, cerebrospinal fluid, and breast milk). Their composition is heterogeneous and depends on the cell type of origin. The unique composition is a prerequisite for its potential function as pathophysiological biomarker. In fact, its specific constitution in transmembrane proteins, soluble proteins, mRNA and microRNA may be representative of a normal physiological or pathological condition. Thus, a critical step for its aplication, in future, as biomarkers consists in the identification of unambiguous correlations between different states of disease progression and their biochemical pattern. Additionally, the possibility to quicky detect and characterize microvesicles and endosomes using specific biosensors, should allow their use in clinical practice as biomarkers of etiological diverse diseases such as cancer, metabolic diseases and neurodegenerative disorders. Beyond its role in the prevention, diagnosis and monitoring of disease progression, they may also play, in the future, an important role in the therapy itself or in monitoring therapeutic success in those diseases that they become physiopathologically implicated.
The microvesicles are a heterogeneous group of spherical vesicles with a diameter of 100-1000 nm formed by budding of the plasma membrane of the cell. The exosomes are more homogeneous and smaller (40-120 nm) structures than the microvesicles. Unlike microvesicles, which are abundant in the blood circulation and derived primarily from platelets, exosomes are originated in the endolysosomal cell compartment. These structures have been detected in the blood and in various body fluids (urine, bronchoalveolar secretions, mucus, saliva, bile, ascyte, cerebrospinal fluid, and breast milk). Their composition is heterogeneous and depends on the cell type of origin. The unique composition is a prerequisite for its potential function as pathophysiological biomarker. In fact, its specific constitution in transmembrane proteins, soluble proteins, mRNA and microRNA may be representative of a normal physiological or pathological condition. Thus, a critical step for its aplication, in future, as biomarkers consists in the identification of unambiguous correlations between different states of disease progression and their biochemical pattern. Additionally, the possibility to quicky detect and characterize microvesicles and endosomes using specific biosensors, should allow their use in clinical practice as biomarkers of etiological diverse diseases such as cancer, metabolic diseases and neurodegenerative disorders. Beyond its role in the prevention, diagnosis and monitoring of disease progression, they may also play, in the future, an important role in the therapy itself or in monitoring therapeutic success in those diseases that they become physiopathologically implicated.
Description
Keywords
MicrovesĂcula Exossoma Biomarcador Doença oncolĂłgica Doença metabĂłlica Microvesicle Exosome Biomarker Oncologic disease Metabolic disease