Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Ageing is an inevitable phenomenon that remains under control of a plethora of signalling pathways and regulatory mechanisms. Slowing of cellular homeostasis and repair pathways, declining genomic and proteomic integrity, and deficient stress regulatory machinery may cause accumulating damage triggering initiation of pathways leading to ageing-associated changes. Multiple genetic studies in small laboratory organisms focused on the manipulation of proteasomal activities have shown promising results in delaying the age-related decline and improving the lifespan. In addition, a number of studies indicate a prominent role of small molecule-based proteasome activators showing positive results in ameliorating the stress conditions, protecting degenerating neurons, restoring cognitive functions, and extending life span of organisms. In this chapter, we provide a brief overview of the multi-enzyme proteasome complex, its structure, subunit composition and variety of cellular functions. We also highlight the strategies applied in the past to modulate the protein degradation efficiency of proteasome and their impact on rebalancing the proteostasis defects. Finally, we provide a descriptive account of proteasome activation mechanisms and small molecule-based strategies to improve the overall organismal health and delay the development of age-associated pathologies.
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Source |
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http://dx.doi.org/10.1007/978-3-031-66768-8_2 | DOI Listing |
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