From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer’s disease
<p dir="ltr">Type 2 Diabetes (T2D) and Alzheimer’s Disease (AD) share common risk factors that can be seen through T2D nearly doubling an individual’s likelihood of developing AD. Some AD patients show signs of metabolic dysfunction as well. This review focuses on the potential mecha...
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| مؤلفون آخرون: | , , , , , , , |
| منشور في: |
2025
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| _version_ | 1864513524560035840 |
|---|---|
| author | Ahmad Raza (18205961) |
| author2 | Shafaq Saleem (22934654) Samar Imran (22997221) Sarah Rahman (4568125) Muhammad Haroon (7830661) Azeen Razzaq (22997224) Ahmad Hussain (22997227) Javed Iqbal (2121922) Brijesh Sathian (479264) |
| author2_role | author author author author author author author author |
| author_facet | Ahmad Raza (18205961) Shafaq Saleem (22934654) Samar Imran (22997221) Sarah Rahman (4568125) Muhammad Haroon (7830661) Azeen Razzaq (22997224) Ahmad Hussain (22997227) Javed Iqbal (2121922) Brijesh Sathian (479264) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ahmad Raza (18205961) Shafaq Saleem (22934654) Samar Imran (22997221) Sarah Rahman (4568125) Muhammad Haroon (7830661) Azeen Razzaq (22997224) Ahmad Hussain (22997227) Javed Iqbal (2121922) Brijesh Sathian (479264) |
| dc.date.none.fl_str_mv | 2025-09-26T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s11011-025-01700-z |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/From_metabolic_dysregulation_to_neurodegenerative_pathology_the_role_of_hyperglycemia_oxidative_stress_and_blood-brain_barrier_breakdown_in_T2D-driven_Alzheimer_s_disease/31056562 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Medical biochemistry and metabolomics Neurosciences Type 2 diabetes mellitus (T2D) Alzheimer’s disease (AD) Insulin resistance Amyloid-beta (Aβ) accumulation Advanced glycation end products (AGEs) Neuroinflammation Mitochondrial dysfunction |
| dc.title.none.fl_str_mv | From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer’s disease |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Type 2 Diabetes (T2D) and Alzheimer’s Disease (AD) share common risk factors that can be seen through T2D nearly doubling an individual’s likelihood of developing AD. Some AD patients show signs of metabolic dysfunction as well. This review focuses on the potential mechanisms associated with these two diseases, like insulin resistance, inflammation, oxidative damage, mitochondrial injury, and cell death. One of the notable elements in this connection is the “brain insulin resistance,” most frequently named as “type 3 diabetes,” which impairs glucose metabolism and facilitates amyloid beta (Aβ) plaque synthesis while reducing the action of insulin-degrading enzyme (IDE). Moreover, the overactivity of glycogen synthase kinase-3 beta (GSK-3β) also triggers taurine protein pathology. Raised concentrations of glucose in blood can produce advanced glycation end products (AGEs), which further exacerbate neuroinflammation in tandem with the mitigation of neurotoxic Aβ oligomers. Inflammation and subsequent damage to mitochondria lead to the dissolution of synapses. Current vascular insults include the breakdown of the blood-brain barrier (BBB) and decreased brain perfusion, along with other contributory factors to conditions conducive to neurotoxicity. Recently, novel therapies are emerging, including GLP-1 agonists, intranasal insulin, and mitochondrial antioxidants, that show surprising results for treating both conditions, but on the contrary, bioavailability and the timing of interventions remain a big challenge in the management of these diseases. Eventually, further research should center on understanding the mechanisms of integration along with the development of molecular biology, neuroimaging, and outcome-driven treatment strategies. Comprehensive strategies that exist between T2D-AD for integration and preservation of brain and metabolic health are addressed in this review.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Metabolic Brain Disease<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s11011-025-01700-z" target="_blank">https://dx.doi.org/10.1007/s11011-025-01700-z</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_2c82e4c0e68e3bf413277973b22ebd05 |
| identifier_str_mv | 10.1007/s11011-025-01700-z |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/31056562 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer’s diseaseAhmad Raza (18205961)Shafaq Saleem (22934654)Samar Imran (22997221)Sarah Rahman (4568125)Muhammad Haroon (7830661)Azeen Razzaq (22997224)Ahmad Hussain (22997227)Javed Iqbal (2121922)Brijesh Sathian (479264)Biomedical and clinical sciencesMedical biochemistry and metabolomicsNeurosciencesType 2 diabetes mellitus (T2D)Alzheimer’s disease (AD)Insulin resistance Amyloid-beta (Aβ) accumulationAdvanced glycation end products (AGEs)NeuroinflammationMitochondrial dysfunction<p dir="ltr">Type 2 Diabetes (T2D) and Alzheimer’s Disease (AD) share common risk factors that can be seen through T2D nearly doubling an individual’s likelihood of developing AD. Some AD patients show signs of metabolic dysfunction as well. This review focuses on the potential mechanisms associated with these two diseases, like insulin resistance, inflammation, oxidative damage, mitochondrial injury, and cell death. One of the notable elements in this connection is the “brain insulin resistance,” most frequently named as “type 3 diabetes,” which impairs glucose metabolism and facilitates amyloid beta (Aβ) plaque synthesis while reducing the action of insulin-degrading enzyme (IDE). Moreover, the overactivity of glycogen synthase kinase-3 beta (GSK-3β) also triggers taurine protein pathology. Raised concentrations of glucose in blood can produce advanced glycation end products (AGEs), which further exacerbate neuroinflammation in tandem with the mitigation of neurotoxic Aβ oligomers. Inflammation and subsequent damage to mitochondria lead to the dissolution of synapses. Current vascular insults include the breakdown of the blood-brain barrier (BBB) and decreased brain perfusion, along with other contributory factors to conditions conducive to neurotoxicity. Recently, novel therapies are emerging, including GLP-1 agonists, intranasal insulin, and mitochondrial antioxidants, that show surprising results for treating both conditions, but on the contrary, bioavailability and the timing of interventions remain a big challenge in the management of these diseases. Eventually, further research should center on understanding the mechanisms of integration along with the development of molecular biology, neuroimaging, and outcome-driven treatment strategies. Comprehensive strategies that exist between T2D-AD for integration and preservation of brain and metabolic health are addressed in this review.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Metabolic Brain Disease<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s11011-025-01700-z" target="_blank">https://dx.doi.org/10.1007/s11011-025-01700-z</a></p>2025-09-26T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s11011-025-01700-zhttps://figshare.com/articles/journal_contribution/From_metabolic_dysregulation_to_neurodegenerative_pathology_the_role_of_hyperglycemia_oxidative_stress_and_blood-brain_barrier_breakdown_in_T2D-driven_Alzheimer_s_disease/31056562CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/310565622025-09-26T09:00:00Z |
| spellingShingle | From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer’s disease Ahmad Raza (18205961) Biomedical and clinical sciences Medical biochemistry and metabolomics Neurosciences Type 2 diabetes mellitus (T2D) Alzheimer’s disease (AD) Insulin resistance Amyloid-beta (Aβ) accumulation Advanced glycation end products (AGEs) Neuroinflammation Mitochondrial dysfunction |
| status_str | publishedVersion |
| title | From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer’s disease |
| title_full | From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer’s disease |
| title_fullStr | From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer’s disease |
| title_full_unstemmed | From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer’s disease |
| title_short | From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer’s disease |
| title_sort | From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer’s disease |
| topic | Biomedical and clinical sciences Medical biochemistry and metabolomics Neurosciences Type 2 diabetes mellitus (T2D) Alzheimer’s disease (AD) Insulin resistance Amyloid-beta (Aβ) accumulation Advanced glycation end products (AGEs) Neuroinflammation Mitochondrial dysfunction |