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Message: fopen(/var/lib/php/sessions/ci_sessionllv9oq9rads7r1dog5vim3qlqmcingc6): Failed to open stream: No space left on device
Filename: drivers/Session_files_driver.php
Line Number: 177
Backtrace:
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)
Filename: Session/Session.php
Line Number: 137
Backtrace:
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 197
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 197
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 271
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 1057
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3175
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Alzheimer's disease (AD) is an age-associated neurodegenerative disorder with a complex etiology. While emerging AD therapeutics can slow cognitive decline, they may worsen dementia in certain groups of individuals. Therefore, alternative treatments are much needed. Microglia, the brain resident macrophages, have the potential to be novel therapeutic targets as they regulate many facets of AD, including lipid droplet (LD) accumulation, amyloid beta (Aβ) clearance, and neuroinflammation. To carry out such functions, microglia undergo phenotypic changes, which are linked to shifts in metabolism and substrate utilization. While homeostatic microglia are driven by oxidative phosphorylation (OXPHOS) and glycolysis, in aging and AD, microglia shift further towards glycolysis. Interestingly, this "metabolic reprogramming" may be linked to an increase in fructose metabolism. In the brain, microglia predominantly express the fructose transporter SLC2A5 (GLUT5), and enzymes involved in fructolysis and endogenous fructose production, with their expression being upregulated in aging and disease. Here, we review evidence for fructose uptake, breakdown, and production in microglia. We also evaluate emerging literature targeting fructose metabolism in the brain and periphery to assess its ability to modulate microglial function in AD. The ability of microglia to transport and utilize fructose, coupled with the well-established role of fructose in metabolic dysfunction, supports the notion that microglial fructose metabolism may be a novel potential therapeutic target for AD.
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Source |
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http://dx.doi.org/10.1186/s12974-025-03401-x | DOI Listing |
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