RESUMO
Complex diseases often involve the interplay between genetic and environmental factors. Charcot-Marie-Tooth type 2 neuropathies (CMT2) are a group of genetically heterogeneous disorders, in which similar peripheral neuropathology is inexplicably caused by various mutated genes. Their possible molecular links remain elusive. Here, we found that upon environmental stress, many CMT2-causing mutant proteins adopt similar properties by entering stress granules (SGs), where they aberrantly interact with G3BP and integrate into SG pathways. For example, glycyl-tRNA synthetase (GlyRS) is translocated from the cytoplasm into SGs upon stress, where the mutant GlyRS perturbs the G3BP-centric SG network by aberrantly binding to G3BP. This disrupts SG-mediated stress responses, leading to increased stress vulnerability in motoneurons. Disrupting this aberrant interaction rescues SG abnormalities and alleviates motor deficits in CMT2D mice. These findings reveal a stress-dependent molecular link across diverse CMT2 mutants and provide a conceptual framework for understanding genetic heterogeneity in light of environmental stress.
Assuntos
Doença de Charcot-Marie-Tooth , Proteínas com Motivo de Reconhecimento de RNA , Grânulos de Estresse , Animais , Camundongos , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/metabolismo , Doença de Charcot-Marie-Tooth/patologia , Citoplasma , Neurônios Motores , Proteínas com Motivo de Reconhecimento de RNA/metabolismoRESUMO
The various tissue damages are a severe problem to human health. The limited human tissue regenerate ability requires suitable biomaterials to help damage tissue repair and regeneration. Therefore, many researchers devoted themselves to exploring biomaterials suitable for tissue repair and regeneration. Polydopamine (PDA) as a natural and multifunctional material which is inspired by mussel has been widely applied in different biomaterials. The excellent properties of PDA, such as strong adhesion, photothermal and high drug-loaded capacity, seem to be born for tissue repair and regeneration. Furthermore, PDA combined with different materials can exert unexpected effects. Thus, to inspire researchers, this review summarizes the recent and representative development of PDA biomaterials in tissue repair and regeneration. This article focuses on why apply PDA in these biomaterials and what PDA can do in different tissue injuries.