Accumulation of amyloid- (A) peptides in the brain has been suggested to be the primary event in sequential progression of Alzheimer's disease (AD). Here, we use Drosophila to examine whether expression of either the human A40 or A42 peptide in the Drosophila brain can induce pathological phenotypes resembling AD. The expression of A42 led to the formation of diffused amyloid deposits, age-dependent learning defects, and extensive neurodegeneration. In contrast, expression of A40 caused only age-dependent learning defects but did not lead to the formation of amyloid deposits or neurodegeneration. These results strongly suggest that accumulation of A42 in the brain is sufficient to cause behavioral deficits and neurodegeneration. Moreover, Drosophila may serve as a model for facilitating the understanding of molecular mechanisms underlying A toxicity and the discovery of novel therapeutic targets for AD. A lzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive decline in memory accompanied by histological changes, including neuronal loss and the formation of neurofibrillary tangles (NFTs) and senile plaques (1). The accumulation of amyloid- (A)42 peptide, the major component of senile plaques, has been hypothesized to be the primary event in AD pathogenesis (2, 3). The strongest support for the A hypothesis comes from genetic analyses of familial AD (FAD); most FAD mutations identified in A precursor protein (APP), Presenilin1 (PS1) and Presenilin2 (PS2) genes appear to cause excessive accumulation of A42 (4). Secretion of A peptides is a result of sequential cleavage of APP by -secretase, a type I transmembrane glycosylated aspartyl protease, and ␥-secretase, a large protein complex that includes at least four proteins, Presenilins (PS1 or PS2), Nicastrin, Aph-1, and Pen-2 (for review, see ref. 5). The heterogeneity of ␥-secretase cleavage gives rise to a series of A peptides, including the major species A40 and a smaller amount of A42.To study AD pathogenesis in vivo, a number of AD mouse models have been established and have successfully recapitulated AD-like phenotypes, including abundant amyloid deposits, astroglial activation, synaptic loss and dysfunction, behavioral abnormalities, and neurodegeneration (6-15). In addition to these mouse models, the model systems that allow highthroughput genetic screening will facilitate the discovery of genes involved in AD pathogenesis. Furthermore, one of the intriguing issues that have not been elucidated in these transgenic mice is the pathological roles of each specific A species (i.e., A40 and A42), because currently available mouse models mainly rely on overexpression of APP.We use a Drosophila model (16) to compare the specific pathological roles of A40 and A42. In Drosophila, all components involved in the protein complex responsible for ␥-secretase activity are highly conserved (17), whereas -secretase activity is absent or very low (18). An APP-like protein (APPL) is also present in flies, althou...
Age-related memory impairment (AMI) is observed in many species. However, it is uncertain whether AMI results from a specific or a nonspecific decay in memory processing. In Drosophila, memory acquired after a single olfactory conditioning paradigm has three distinct phases: short-term memory (STM), middle-term memory (MTM), and longer-lasting anesthesia-resistant memory (ARM). Here, we demonstrate that age-related defects in olfactory memory are identical to those of the MTM mutant amnesiac (amn). Furthermore, amn flies do not exhibit an age-dependent decrease in memory, in contrast to other memory mutants. The absence of AMI in amn flies is restored by expression of an amn transgene predominantly in DPM cells. Thus, we propose that AMI in flies results from a specific decrease in amn-dependent MTM.
Background. Frozen shoulder (FS) is associated with pain, reduced range of motion (ROM), and shoulder function. The condition occurs in 2–5% of the population, and it is especially common around the age of 50 years. FS symptoms will recover after 1–4 years. Many patients turn to acupuncture in order to alleviate the FS symptoms. Objective. In this review, we will investigate the efficiency of acupuncture as a FS treatment. Methods. A literature search of acupuncture and FS-related keywords was performed in the following databases: PubMed, Cochrane Library, Embase, and Web of Science. Thirteen publications were included for a systematic review, and a meta-analysis was done using the following measurements: visual analogue scale (VAS) for pain, Constant-Murley Shoulder Outcome Score (CMS) for shoulder function, and active shoulder ROM including flexion, abduction, and external rotation. The Cochrane Collaboration’s risk of bias tool and quality of evidence GRADE recommendations and STRICTA 2010 were used to grade the included publications. Results. A meta-analysis on VAS pain score showed significant pain reduction, restoring CMS shoulder function, and flexion ROM in favor of acupuncture versus the control. In external rotation and abduction ROM, a meta-analysis was not significant. The most used acupoints are Jian Yu (LI15) and Jian Liao (TB14). Conclusions. The results indicate that acupuncture could be safe and effective for pain reduction, restoring shoulder function, and restoring flexion ROM for FS patients in the short term and midterm. However, the level of evidence was very low. More high-quality and longer studies are needed in order to robust the evidence.
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