The Collagen Chaperone HSP47 Is a New Interactor of APP that Affects the Levels of Extracellular Beta-Amyloid Peptides

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Aβ peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Aβ peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques

Movement Patterns and Muscular Function Before and After Onset of Sports-Related Groin Pain: A Systematic Review with Meta-analysis

BACKGROUND: Sports-related groin pain (SRGP) is a common entity in rotational sports such as football, rugby and hockey, accounting for 12-18 % of injuries each year, with high recurrence rates and often prolonged time away from sport. OBJECTIVE: This systematic review synthesises movement and muscle function findings to better understand deficits and guide rehabilitation. STUDY SELECTION: Prospective and retrospective cross-sectional studies investigating muscle strength, flexibility, cross-sectional area, electromyographic activation onset and magnitude in patients with SRGP were included. SEARCH METHODS: Four databases (MEDLINE, Web of Knowledge, EBSCOhost and EMBASE) were searched in June 2014. Studies were critiqued using a modified version of the Downs and Black Quality Index, and a meta-analysis was performed. RESULTS: Seventeen studies (14 high quality, 3 low quality; 8 prospective and 9 retrospective) were identified. Prospective findings: moderate evidence indicated decreased hip abduction flexibility as a risk factor for SRGP. Limited or very limited evidence suggested that decreased hip adduction strength during isokinetic testing at ~119°/s was a risk factor for SRGP, but no associations were found at ~30°/s or ~210°/s, or with peak torque angle. Decreased hip abductor strength in angular velocity in ~30°/s but not in ~119°/s and ~210°/s was found as a risk factor for SRGP. No relationships were found with hip internal or external rotation range of movement, nor isokinetic knee extension strength. Decreased isokinetic knee flexion strength also was a potential risk factor for SRGP, at a speed ~60°/s. Retrospective findings: there was strong evidence of decreased hip adductor muscle strength during a squeeze test at 45°, and decreased total hip external rotation range of movement (sum of both legs) being associated with SRGP. There was strong evidence of no relationship to abductor muscle strength nor unilateral hip internal and external rotation range of movement. Moderate evidence suggested that increased abduction flexibility and no change in total hip internal rotation range of movement (sum of both legs) were retrospectively associated with SRGP. Limited or very limited evidence (significant findings only) indicated decreased hip adductor muscle strength during 0° and 30° squeeze tests and during an eccentric hip adduction test, but a decrease in the isometric adductors-to-abductors strength ratio at speed 120°/s; decreased abductors-to-adductors activation ratio in the early phase in the moving leg as well as in all three phases in the weight-bearing leg during standing hip flexion; and increased hip flexors strength during isokinetic and decrease in transversus abdominis muscle resting thickness associated with SRGP. CONCLUSIONS: There were a number of significant movement and muscle function associations observed in athletes both prior to and following the onset of SRGP. The strength of findings was hampered by the lack of consistent terminology and diagnostic criteria, with there being clear guides for future research. Nonetheless, these findings should be considered in rehabilitation and prevention planning