Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

Improving the entire outpatient clinic experience is an important measure in the new era to enhance patients'sense of gain from medical treatment.Beijing Tongren Hospital Affiliated to Capital Medical University explores the establishment of a full-process outpatient service management system based on continuous improvement of medical services.Through the concept of forward service,it focuses on the patient's pre-diagnosis experience;the process is simplified and intelligently guided to optimize the patient's in-diagnosis experience;and continuous diagnosis and treatment Model innovation improves patients'post-diagnosis experience and creates a Chinese-style modern outpatient medical service model to continuously meet the people's growing needs for a better life.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Improving the entire outpatient clinic experience is an important measure in the new era to enhance patients'sense of gain from medical treatment.Beijing Tongren Hospital Affiliated to Capital Medical University explores the establishment of a full-process outpatient service management system based on continuous improvement of medical services.Through the concept of forward service,it focuses on the patient's pre-diagnosis experience;the process is simplified and intelligently guided to optimize the patient's in-diagnosis experience;and continuous diagnosis and treatment Model innovation improves patients'post-diagnosis experience and creates a Chinese-style modern outpatient medical service model to continuously meet the people's growing needs for a better life.

Improving the entire outpatient clinic experience is an important measure in the new era to enhance patients'sense of gain from medical treatment.Beijing Tongren Hospital Affiliated to Capital Medical University explores the establishment of a full-process outpatient service management system based on continuous improvement of medical services.Through the concept of forward service,it focuses on the patient's pre-diagnosis experience;the process is simplified and intelligently guided to optimize the patient's in-diagnosis experience;and continuous diagnosis and treatment Model innovation improves patients'post-diagnosis experience and creates a Chinese-style modern outpatient medical service model to continuously meet the people's growing needs for a better life.

Improving the entire outpatient clinic experience is an important measure in the new era to enhance patients'sense of gain from medical treatment.Beijing Tongren Hospital Affiliated to Capital Medical University explores the establishment of a full-process outpatient service management system based on continuous improvement of medical services.Through the concept of forward service,it focuses on the patient's pre-diagnosis experience;the process is simplified and intelligently guided to optimize the patient's in-diagnosis experience;and continuous diagnosis and treatment Model innovation improves patients'post-diagnosis experience and creates a Chinese-style modern outpatient medical service model to continuously meet the people's growing needs for a better life.

Improving the entire outpatient clinic experience is an important measure in the new era to enhance patients'sense of gain from medical treatment.Beijing Tongren Hospital Affiliated to Capital Medical University explores the establishment of a full-process outpatient service management system based on continuous improvement of medical services.Through the concept of forward service,it focuses on the patient's pre-diagnosis experience;the process is simplified and intelligently guided to optimize the patient's in-diagnosis experience;and continuous diagnosis and treatment Model innovation improves patients'post-diagnosis experience and creates a Chinese-style modern outpatient medical service model to continuously meet the people's growing needs for a better life.

Improving the entire outpatient clinic experience is an important measure in the new era to enhance patients'sense of gain from medical treatment.Beijing Tongren Hospital Affiliated to Capital Medical University explores the establishment of a full-process outpatient service management system based on continuous improvement of medical services.Through the concept of forward service,it focuses on the patient's pre-diagnosis experience;the process is simplified and intelligently guided to optimize the patient's in-diagnosis experience;and continuous diagnosis and treatment Model innovation improves patients'post-diagnosis experience and creates a Chinese-style modern outpatient medical service model to continuously meet the people's growing needs for a better life.

Improving the entire outpatient clinic experience is an important measure in the new era to enhance patients'sense of gain from medical treatment.Beijing Tongren Hospital Affiliated to Capital Medical University explores the establishment of a full-process outpatient service management system based on continuous improvement of medical services.Through the concept of forward service,it focuses on the patient's pre-diagnosis experience;the process is simplified and intelligently guided to optimize the patient's in-diagnosis experience;and continuous diagnosis and treatment Model innovation improves patients'post-diagnosis experience and creates a Chinese-style modern outpatient medical service model to continuously meet the people's growing needs for a better life.

Improving the entire outpatient clinic experience is an important measure in the new era to enhance patients'sense of gain from medical treatment.Beijing Tongren Hospital Affiliated to Capital Medical University explores the establishment of a full-process outpatient service management system based on continuous improvement of medical services.Through the concept of forward service,it focuses on the patient's pre-diagnosis experience;the process is simplified and intelligently guided to optimize the patient's in-diagnosis experience;and continuous diagnosis and treatment Model innovation improves patients'post-diagnosis experience and creates a Chinese-style modern outpatient medical service model to continuously meet the people's growing needs for a better life.