It is well recognized that mitochondrial dysfunction contributes to neurodegeneration occurring in Alzheimer’s disease (AD). However, evidences of mitochondrial defects in AD peripheral cells are still inconclusive. Here, some mitochondrial-encoded and nuclear-encoded proteins, involved in maintaining the correct mitochondria machine, were investigated in term of protein expression and enzymatic activity in peripheral blood mononuclear cells (PBMCs) isolated from AD, Mild Cognitive Impairment (MCI) patients and healthy subjects. In addition mitochondrial DNA copy number was measured by real time PCR. We found some differences and some similarities between AD and MCI when compared with healthy subjects. For example, cytochrome C and cytochrome B were decreased in AD, while MCI showed only a statistical reduction of cytochrome C. On the other hand, both AD and MCI blood cells exhibited high nitrated MnSOD, index of a pro-oxidant environment inside the mitochondria. TFAM, a regulator of mitochondrial genome replication and transcription, was decreased in both AD and MCI blood cells. Moreover also the mitochondrial DNA amount was reduced in PBMCs from both patient groups. In conclusion these data confirmed peripheral mitochondria impairment in AD, and demonstrated that TFAM and mtDNA amount reduction could be two features of early events occurring in AD pathogenesis.

Mitochondrial Alterations in Peripherla Mononuclear Blood Cells from Alzheimer's Disease and Mild Cognitive Impairment Patients

DELBARBA, ANDREA;ABATE, GIULIA;PRANDELLI, Chiara;MARZIANO, MARIAGRAZIA;BUIZZA, Laura;MEMO, Maurizio;UBERTI, Daniela Letizia
2016

Abstract

It is well recognized that mitochondrial dysfunction contributes to neurodegeneration occurring in Alzheimer’s disease (AD). However, evidences of mitochondrial defects in AD peripheral cells are still inconclusive. Here, some mitochondrial-encoded and nuclear-encoded proteins, involved in maintaining the correct mitochondria machine, were investigated in term of protein expression and enzymatic activity in peripheral blood mononuclear cells (PBMCs) isolated from AD, Mild Cognitive Impairment (MCI) patients and healthy subjects. In addition mitochondrial DNA copy number was measured by real time PCR. We found some differences and some similarities between AD and MCI when compared with healthy subjects. For example, cytochrome C and cytochrome B were decreased in AD, while MCI showed only a statistical reduction of cytochrome C. On the other hand, both AD and MCI blood cells exhibited high nitrated MnSOD, index of a pro-oxidant environment inside the mitochondria. TFAM, a regulator of mitochondrial genome replication and transcription, was decreased in both AD and MCI blood cells. Moreover also the mitochondrial DNA amount was reduced in PBMCs from both patient groups. In conclusion these data confirmed peripheral mitochondria impairment in AD, and demonstrated that TFAM and mtDNA amount reduction could be two features of early events occurring in AD pathogenesis.
File in questo prodotto:
File Dimensione Formato  
MANUSCRIPT OXIDATIVE MED AND CELL LONGEVITY REV .pdf

gestori archivio

Tipologia: Documento in Pre-print
Licenza: PUBBLICO - Pubblico con Copyright
Dimensione 1.56 MB
Formato Adobe PDF
1.56 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
5923938.pdf

accesso aperto

Tipologia: Full Text
Licenza: Dominio pubblico
Dimensione 2.17 MB
Formato Adobe PDF
2.17 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11379/464050
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 35
  • ???jsp.display-item.citation.isi??? 35
social impact