PMID- 34439505
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210830
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 10
IP  - 8
DP  - 2021 Aug 6
TI  - Diabetes and Alzheimer's Disease: Might Mitochondrial Dysfunction Help 
      Deciphering the Common Path?
LID - 10.3390/antiox10081257 [doi]
LID - 1257
AB  - A growing number of clinical and epidemiological studies support the hypothesis 
      of a tight correlation between type 2 diabetes mellitus (T2DM) and the 
      development risk of Alzheimer's disease (AD). Indeed, the proposed definition of 
      Alzheimer's disease as type 3 diabetes (T3D) underlines the key role played by 
      deranged insulin signaling to accumulation of aggregated amyloid beta (Abeta) 
      peptides in the senile plaques of the brain. Metabolic disturbances such as 
      hyperglycemia, peripheral hyperinsulinemia, dysregulated lipid metabolism, and 
      chronic inflammation associated with T2DM are responsible for an inefficient 
      transport of insulin to the brain, producing a neuronal insulin resistance that 
      triggers an enhanced production and deposition of Abeta and concomitantly 
      contributes to impairment in the micro-tubule-associated protein Tau, leading to 
      neural degeneration and cognitive decline. Furthermore, the reduced antioxidant 
      capacity observed in T2DM patients, together with the impairment of cerebral 
      glucose metabolism and the decreased performance of mitochondrial activity, 
      suggests the existence of a relationship between oxidative damage, mitochondrial 
      impairment, and cognitive dysfunction that could further reinforce the common 
      pathophysiology of T2DM and AD. In this review, we discuss the molecular 
      mechanisms by which insulin-signaling dysregulation in T2DM can contribute to the 
      pathogenesis and progression of AD, deepening the analysis of complex mechanisms 
      involved in reactive oxygen species (ROS) production under oxidative stress and 
      their possible influence in AD and T2DM. In addition, the role of current 
      therapies as tools for prevention or treatment of damage induced by oxidative 
      stress in T2DM and AD will be debated.
FAU - Potenza, Maria Assunta
AU  - Potenza MA
AD  - Department of Biomedical Sciences and Human Oncology-Section of Pharmacology, 
      Medical School, University of Bari "Aldo Moro", Polyclinic University Hospital of 
      Bari, p.zza G. Cesare 11, 70124 Bari, Italy.
FAU - Sgarra, Luca
AU  - Sgarra L
AD  - Department of Biomedical Sciences and Human Oncology-Section of Pharmacology, 
      Medical School, University of Bari "Aldo Moro", Polyclinic University Hospital of 
      Bari, p.zza G. Cesare 11, 70124 Bari, Italy.
FAU - Desantis, Vanessa
AU  - Desantis V
AUID- ORCID: 0000-0003-1942-2601
AD  - Department of Biomedical Sciences and Human Oncology-Section of Pharmacology, 
      Medical School, University of Bari "Aldo Moro", Polyclinic University Hospital of 
      Bari, p.zza G. Cesare 11, 70124 Bari, Italy.
FAU - Nacci, Carmela
AU  - Nacci C
AD  - Department of Biomedical Sciences and Human Oncology-Section of Pharmacology, 
      Medical School, University of Bari "Aldo Moro", Polyclinic University Hospital of 
      Bari, p.zza G. Cesare 11, 70124 Bari, Italy.
FAU - Montagnani, Monica
AU  - Montagnani M
AUID- ORCID: 0000-0002-5697-8185
AD  - Department of Biomedical Sciences and Human Oncology-Section of Pharmacology, 
      Medical School, University of Bari "Aldo Moro", Polyclinic University Hospital of 
      Bari, p.zza G. Cesare 11, 70124 Bari, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210806
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC8389322
OTO - NOTNLM
OT  - Alzheimer's disease (AD)
OT  - mitochondrial dysfunction
OT  - type 2 diabetes (T2DM)
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/28 06:00
MHDA- 2021/08/28 06:01
PMCR- 2021/08/06
CRDT- 2021/08/27 01:04
PHST- 2021/07/05 00:00 [received]
PHST- 2021/08/03 00:00 [revised]
PHST- 2021/08/04 00:00 [accepted]
PHST- 2021/08/27 01:04 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/08/28 06:01 [medline]
PHST- 2021/08/06 00:00 [pmc-release]
AID - antiox10081257 [pii]
AID - antioxidants-10-01257 [pii]
AID - 10.3390/antiox10081257 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2021 Aug 6;10(8):1257. doi: 10.3390/antiox10081257.