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@ARTICLE{Ayoub:281646,
author = {Ayoub, Sama and Arabi, Maryam and Al-Najjar, Yousef and
Laswi, Ibrahim and Outeiro, Tiago F and Chaari, Ali},
title = {{G}lycation in {A}lzheimer's {D}isease and {T}ype 2
{D}iabetes: {T}he {P}rospect of {D}ual {D}rug {A}pproaches
for {T}herapeutic {I}nterventions.},
journal = {Molecular neurobiology},
volume = {62},
number = {11},
issn = {0893-7648},
address = {Totowa, NJ},
publisher = {Humana Press},
reportid = {DZNE-2025-01164},
pages = {14859 - 14882},
year = {2025},
abstract = {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.},
subtyp = {Review Article},
keywords = {Alzheimer Disease: drug therapy / Alzheimer Disease:
metabolism / Humans / Diabetes Mellitus, Type 2: drug
therapy / Diabetes Mellitus, Type 2: metabolism / Glycation
End Products, Advanced: metabolism / Animals / Hypoglycemic
Agents: therapeutic use / Hypoglycemic Agents: pharmacology
/ Gastrointestinal Microbiome: drug effects / Advanced
glycation end products (AGEs) (Other) / Alzheimer’s
disease (Other) / Dual drugs (Other) / Type 2 diabetes
(Other) / Glycation End Products, Advanced (NLM Chemicals) /
Hypoglycemic Agents (NLM Chemicals)},
cin = {AG Fischer},
ddc = {570},
cid = {I:(DE-2719)1410002},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40402411},
doi = {10.1007/s12035-025-05051-9},
url = {https://pub.dzne.de/record/281646},
}