As a member of the A Disintegrin And Metalloproteinase (ADAM) family, ADAM10 has been identified as the constitutive α-secretase in the process of amyloid-β protein precursor (AβPP) cleavage and plays a critical role in reducing the generation of the amyloid-β (Aβ) peptides. Recent studies have demonstrated its beneficial role in alleviating the pathologic impairment in Alzheimer's disease (AD) both in vitro and in vivo. However, the role of ADAM10 in AD and the underlying molecular mechanisms are still not well established. Increasing evidence indicates that ADAM10 not only reduces the generation of Aβ but may also affect the pathology of AD through potential mechanisms including reducing tau pathology, maintaining normal synaptic functions, and promoting hippocampal neurogenesis and the homeostasis of neuronal networks. Mechanistically, ADAM10 regulates these functions by interacting with postsynaptic substrates in brain, especially synaptic cell receptors and adhesion molecules. Furthermore, ADAM10 protein in platelets seems to be a promising biomarker for AD diagnosis. This review will summarize the role of ADAM10 in AD and highlight its functions besides its role as the α-secretase in AβPP cleavage. Meanwhile, we will discuss the therapeutic potential of ADAM10 in treating AD.
Abstract. Accumulating evidence suggests that smoking is associated with diabetic foot amputation. However, the currently available results are inconsistent and controversial. Therefore, the present study performed a meta-analysis to systematically review the association between smoking and diabetic foot amputation and to investigate the risk factors of diabetic foot amputation. Public databases, including PubMed and Embase, were searched prior to 29th February 2016. The heterogeneity was assessed using the Cochran's Q statistic and the I 2 statistic, and odds ratio (OR) and 95% confidence interval (CI) were calculated and pooled appropriately. Sensitivity analysis was performed to evaluate the stability of the results. In addition, Egger's test was applied to assess any potential publication bias. Based on the research, a total of eight studies, including five cohort studies and three case control studies were included. The data indicated that smoking significantly increased the risk of diabetic foot amputation (OR=1.65; 95% CI, 1.09-2.50; P<0.0001) compared with non-smoking. Sensitivity analysis demonstrated that the pooled analysis did not vary substantially following the exclusion of any one study. Additionally, there was no evidence of publication bias (Egger's test, t=0.1378; P=0.8958). Furthermore, no significant difference was observed between the minor and major amputation groups in patients who smoked (OR=0.79; 95% CI, 0.24-2.58). The results of the present meta-analysis suggested that smoking is a notable risk factor for diabetic foot amputation. Smoking cessation appears to reduce the risk of diabetic foot amputation.
Background: The sequence effect (SE), referring to step-to-step reduction in amplitude, is considered to lead to freezing of gait (FOG) in Parkinson's disease (PD). Visual cues may alleviate SE and help reduce freezing episodes. FOG patients show significant SE prior to turning or toward a doorway, but the SE toward a destination has not been clearly studied. Objectives: To examine the SE when approaching a destination in PD patients with FOG, and to further explore the effects of different types of visual cues on destination SE. Methods: Thirty-five PD patients were divided into a freezing (PD+FOG, n = 15) group and a non-freezing (PD-FOG, n = 20) group. Walking trials were tested under three conditions, including without cues (no-cue condition), with wearable laser lights (laser condition), and with transverse strips placed on the floor (strip condition). Kinematic data was recorded by a portable Inertial Measurement Unit (IMU) system. The destination SE and some key gait parameters were evaluated. Results: The PD+FOG group showed greater destination SE in the no-cue and laser conditions when compared to the PD-FOG group. There were no significant differences in the strip condition when comparing destination SE of the two groups. The destination SE was alleviated only by using the transverse strips on the floor. In contrast, transverse strips and wearable laser lights could increase the step length. Conclusions: The significant destination SE may explain why FOG patients are prone to freezing when heading toward their destination. Visual cues using transverse strips on the floor may be a more effective strategy for FOG rehabilitation in PD patients.
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