RESUMO
Background: Difficulty in modulating multisensory input, specifically the sensory over-responsive (SOR) type, is linked to pain hypersensitivity and anxiety, impacting daily function and quality of life in children and adults. Reduced cortical activity recorded under resting state has been reported, suggestive of neuromodulation as a potential therapeutic modality. This feasibility study aimed to explore neurofeedback intervention in SOR. Methods: Healthy women with SOR (n = 10) underwent an experimental feasibility study comprising four measurement time points (T1baseline; T2preintervention; T3postintervention; T4follow-up). Outcome measures included resting-state EEG recording, in addition to behavioral assessments of life satisfaction, attaining functional goals, pain sensitivity, and anxiety. Intervention targeted the upregulation of alpha oscillatory power over ten sessions. Results: No changes were detected in all measures between T1 and T2. Exploring the changes in brain activity between T2 and T4 revealed power enhancement in delta, theta, beta, and gamma oscillatory bands, detected in the frontal region (p = 0.03−<0.001; Cohen's d = 0.637−1.126) but not in alpha oscillations. Furthermore, a large effect was found in enhancing life satisfaction and goal attainment (Cohen's d = 1.18; 1.04, respectively), and reduced pain sensitivity and anxiety trait (Cohen's d = 0.70). Conclusion: This is the first study demonstrating the feasibility of neurofeedback intervention in SOR.
Assuntos
Neurorretroalimentação , Adulto , Transtornos de Ansiedade , Criança , Estudos de Viabilidade , Feminino , Lobo Frontal , Humanos , Neurorretroalimentação/fisiologia , Qualidade de VidaRESUMO
The highly conserved COP9 signalosome (CSN) complex is a key regulator of all cullin-RING-ubiquitin ligases (CRLs), the largest family of E3 ubiquitin ligases. Until now, it was accepted that the CSN is composed of eight canonical components. Here, we report the discovery of an additional integral and stoichiometric subunit that had thus far evaded detection, and we named it CSNAP (CSN acidic protein). We show that CSNAP binds CSN3, CSN5, and CSN6, and its incorporation into the CSN complex is mediated through the C-terminal region involving conserved aromatic residues. Moreover, depletion of this small protein leads to reduced proliferation and a flattened and enlarged morphology. Finally, on the basis of sequence and structural properties shared by both CSNAP and DSS1, a component of the related 19S lid proteasome complex, we propose that CSNAP, the ninth CSN subunit, is the missing paralogous subunit of DSS1.
Assuntos
Proteínas de Transporte/metabolismo , Complexos Multiproteicos/metabolismo , Peptídeo Hidrolases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Sequência de Aminoácidos , Complexo do Signalossomo COP9 , Proteínas de Transporte/química , Proteínas de Transporte/genética , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Dados de Sequência Molecular , Complexos Multiproteicos/química , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Peptídeo Hidrolases/química , Ligação Proteica , Proteínas Quinases/química , Proteínas Quinases/metabolismo , Multimerização ProteicaRESUMO
The Parkinson's-associated protein, DJ-1, is a highly conserved homodimer, ubiquitously expressed in cells. Here we demonstrate that DJ-1 is a 20S proteasome regulator. We show that DJ-1 physically binds the 20S proteasome and inhibits its activity, rescuing partially unfolded proteins from degradation. Consequently, DJ-1 stabilizes the cellular levels of 20S proteasome substrates, as we show for α-synuclein and p53. Furthermore, we demonstrate that following oxidative stress, DJ-1 is involved in the Nrf2-dependent oxidative stress response that leads to the upregulation of both the 20S proteasome and its regulator, NQO1. Overall, our results suggest a regulatory circuit in which DJ-1, under conditions of oxidative stress, both upregulates and inhibits the 20S proteasome, providing a rigorous control mechanism at a time when the 20S proteasome becomes the major proteolytic machinery. Such a tight regulation of the 20S proteasome may sustain the balance between the need to rapidly eliminate oxidatively damaged proteins and maintain the abundance of native, intrinsically unstructured proteins, which coordinate regulatory and signalling events.