Dysfunction of Mitochondria in Alzheimer’s Disease: ANT and VDAC Interact with Toxic Proteins and Aid to Determine the Fate of Brain Cells
Alzheimer’s disease (AD), certainly the most widespread proteinopathy, has as classical neuropathological hallmarks, two groups of protein aggregates: senile plaques and neurofibrillary tangles. However, the research interest is rapidly gaining ground in a better understanding of other pathological...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/14/7722 |
| _version_ | 1797433536847806464 |
|---|---|
| author | Anna Atlante Daniela Valenti Valentina Latina Giuseppina Amadoro |
| author_facet | Anna Atlante Daniela Valenti Valentina Latina Giuseppina Amadoro |
| author_sort | Anna Atlante |
| collection | DOAJ |
| description | Alzheimer’s disease (AD), certainly the most widespread proteinopathy, has as classical neuropathological hallmarks, two groups of protein aggregates: senile plaques and neurofibrillary tangles. However, the research interest is rapidly gaining ground in a better understanding of other pathological features, first, of all the mitochondrial dysfunctions. Several pieces of evidence support the hypothesis that abnormal mitochondrial function may trigger aberrant processing of amyloid progenitor protein or tau and thus neurodegeneration. Here, our aim is to emphasize the role played by two ‘bioenergetic’ proteins inserted in the mitochondrial membranes, inner and outer, respectively, that is, the adenine nucleotide translocator (ANT) and the voltage-dependent anion channel (VDAC), in the progression of AD. To perform this, we will magnify the ANT and VDAC defects, which are measurable hallmarks of mitochondrial dysfunction, and collect all the existing information on their interaction with toxic Alzheimer’s proteins. The pathological convergence of tau and amyloid β-peptide (Aβ) on mitochondria may finally explain why the therapeutic strategies used against the toxic forms of Aβ or tau have not given promising results separately. Furthermore, the crucial role of ANT-1 and VDAC impairment in the onset/progression of AD opens a window for new therapeutic strategies aimed at preserving/improving mitochondrial function, which is suspected to be the driving force leading to plaque and tangle deposition in AD. |
| first_indexed | 2024-03-09T10:17:21Z |
| format | Article |
| id | doaj.art-76c5031a60cc4ae88c92783413bf6797 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T10:17:21Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-76c5031a60cc4ae88c92783413bf67972023-12-01T22:14:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314772210.3390/ijms23147722Dysfunction of Mitochondria in Alzheimer’s Disease: ANT and VDAC Interact with Toxic Proteins and Aid to Determine the Fate of Brain CellsAnna Atlante0Daniela Valenti1Valentina Latina2Giuseppina Amadoro3Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM)-CNR, Via G. Amendola122/O, 70126 Bari, ItalyInstitute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM)-CNR, Via G. Amendola122/O, 70126 Bari, ItalyEuropean Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, ItalyInstitute of Translational Pharmacology (IFT)-CNR, Via Fosso del Cavaliere 100, 00133 Rome, ItalyAlzheimer’s disease (AD), certainly the most widespread proteinopathy, has as classical neuropathological hallmarks, two groups of protein aggregates: senile plaques and neurofibrillary tangles. However, the research interest is rapidly gaining ground in a better understanding of other pathological features, first, of all the mitochondrial dysfunctions. Several pieces of evidence support the hypothesis that abnormal mitochondrial function may trigger aberrant processing of amyloid progenitor protein or tau and thus neurodegeneration. Here, our aim is to emphasize the role played by two ‘bioenergetic’ proteins inserted in the mitochondrial membranes, inner and outer, respectively, that is, the adenine nucleotide translocator (ANT) and the voltage-dependent anion channel (VDAC), in the progression of AD. To perform this, we will magnify the ANT and VDAC defects, which are measurable hallmarks of mitochondrial dysfunction, and collect all the existing information on their interaction with toxic Alzheimer’s proteins. The pathological convergence of tau and amyloid β-peptide (Aβ) on mitochondria may finally explain why the therapeutic strategies used against the toxic forms of Aβ or tau have not given promising results separately. Furthermore, the crucial role of ANT-1 and VDAC impairment in the onset/progression of AD opens a window for new therapeutic strategies aimed at preserving/improving mitochondrial function, which is suspected to be the driving force leading to plaque and tangle deposition in AD.https://www.mdpi.com/1422-0067/23/14/7722Alzheimer’s diseasemitochondriaamyloid β-peptidetaumitochondrial respiratory chainadenine nucleotide translocator |
| spellingShingle | Anna Atlante Daniela Valenti Valentina Latina Giuseppina Amadoro Dysfunction of Mitochondria in Alzheimer’s Disease: ANT and VDAC Interact with Toxic Proteins and Aid to Determine the Fate of Brain Cells International Journal of Molecular Sciences Alzheimer’s disease mitochondria amyloid β-peptide tau mitochondrial respiratory chain adenine nucleotide translocator |
| title | Dysfunction of Mitochondria in Alzheimer’s Disease: ANT and VDAC Interact with Toxic Proteins and Aid to Determine the Fate of Brain Cells |
| title_full | Dysfunction of Mitochondria in Alzheimer’s Disease: ANT and VDAC Interact with Toxic Proteins and Aid to Determine the Fate of Brain Cells |
| title_fullStr | Dysfunction of Mitochondria in Alzheimer’s Disease: ANT and VDAC Interact with Toxic Proteins and Aid to Determine the Fate of Brain Cells |
| title_full_unstemmed | Dysfunction of Mitochondria in Alzheimer’s Disease: ANT and VDAC Interact with Toxic Proteins and Aid to Determine the Fate of Brain Cells |
| title_short | Dysfunction of Mitochondria in Alzheimer’s Disease: ANT and VDAC Interact with Toxic Proteins and Aid to Determine the Fate of Brain Cells |
| title_sort | dysfunction of mitochondria in alzheimer s disease ant and vdac interact with toxic proteins and aid to determine the fate of brain cells |
| topic | Alzheimer’s disease mitochondria amyloid β-peptide tau mitochondrial respiratory chain adenine nucleotide translocator |
| url | https://www.mdpi.com/1422-0067/23/14/7722 |
| work_keys_str_mv | AT annaatlante dysfunctionofmitochondriainalzheimersdiseaseantandvdacinteractwithtoxicproteinsandaidtodeterminethefateofbraincells AT danielavalenti dysfunctionofmitochondriainalzheimersdiseaseantandvdacinteractwithtoxicproteinsandaidtodeterminethefateofbraincells AT valentinalatina dysfunctionofmitochondriainalzheimersdiseaseantandvdacinteractwithtoxicproteinsandaidtodeterminethefateofbraincells AT giuseppinaamadoro dysfunctionofmitochondriainalzheimersdiseaseantandvdacinteractwithtoxicproteinsandaidtodeterminethefateofbraincells |