TY  - JOUR
AU  - Ayoub, Sama
AU  - Arabi, Maryam
AU  - Al-Najjar, Yousef
AU  - Laswi, Ibrahim
AU  - Outeiro, Tiago F
AU  - Chaari, Ali
TI  - Glycation in Alzheimer's Disease and Type 2 Diabetes: The Prospect of Dual Drug Approaches for Therapeutic Interventions.
JO  - Molecular neurobiology
VL  - 62
IS  - 11
SN  - 0893-7648
CY  - Totowa, NJ
PB  - Humana Press
M1  - DZNE-2025-01164
SP  - 14859 - 14882
PY  - 2025
AB  - As global life expectancy increases, the prevalence of neurodegenerative diseases like Alzheimer's disease (AD) continues to rise. Since therapeutic options are minimal, a deeper understanding of the pathophysiology is essential for improved diagnosis and treatments. AD is marked by the aggregation of Aβ proteins, tau hyperphosphorylation, and progressive neuronal loss, though its precise origins remain poorly understood. Meanwhile, type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia, leading to the formation of advanced glycation end products (AGEs), which are implicated in tissue damage and neurotoxicity. These AGEs can be resistant to proteolysis and, therefore, accumulate, exacerbating AD pathology and accelerating neurodegeneration. Insulin resistance, a hallmark of T2DM, further complicates AD pathogenesis by promoting tau hyperphosphorylation and Aβ plaque accumulation. Additionally, gut microbiome dysbiosis in T2DM fosters AGE accumulation and neuroinflammation, underscoring the intricate relationship between metabolic disorders, gut health, and neurodegenerative processes. This complex interplay presents both a challenge and a potential avenue for therapeutic intervention. Emerging evidence suggests that antidiabetic medications may offer cognitive benefits in AD, as well as in other neurodegenerative conditions, pointing to a shared pathophysiology. Thus, we posit that targeting AGEs, insulin signaling, and gut microbiota dynamics presents promising opportunities for innovative treatment approaches in AD and T2DM.
KW  - Alzheimer Disease: drug therapy
KW  - Alzheimer Disease: metabolism
KW  - Humans
KW  - Diabetes Mellitus, Type 2: drug therapy
KW  - Diabetes Mellitus, Type 2: metabolism
KW  - Glycation End Products, Advanced: metabolism
KW  - Animals
KW  - Hypoglycemic Agents: therapeutic use
KW  - Hypoglycemic Agents: pharmacology
KW  - Gastrointestinal Microbiome: drug effects
KW  - Advanced glycation end products (AGEs) (Other)
KW  - Alzheimer’s disease (Other)
KW  - Dual drugs (Other)
KW  - Type 2 diabetes (Other)
KW  - Glycation End Products, Advanced (NLM Chemicals)
KW  - Hypoglycemic Agents (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40402411
DO  - DOI:10.1007/s12035-025-05051-9
UR  - https://pub.dzne.de/record/281646
ER  -