Table 1.
Mitochondria AAV based therapeutics in Alzheimer's disease.
| AAV-Protein | Protein function | Model | Effects | Reference |
|---|---|---|---|---|
| AAV9-NDI1 | Yeast mitochondrial NADH dehydrogenase; electron transport chain; apoptosis | SH-SY5Y Aβ1-42 cell model, Aβ1-42 hippocampal injected mice. |
Restored oxidative phosphorylation; reduces ROS production | Li et al., 2024 |
| AAV9-DJ-1 | Regulation of apoptosis; PINK1/parkin-mediated mitophagy; Antioxidant response through NRF2 activation |
APP/PS1 | Enhanced cognitive function; increased levels of antioxidant genes (NRF2, SOD, GPx) | Peng et al., 2023 |
| AAV-Trx-1 | Maintains redox homeostasis; Antioxidant ROS scavenger |
APP/PS1 | Improved learning and memory; Reduced hippocampal Aβ deposition; increased expression of APRK, Sirt1, PGC-1α |
Jia et al., 2023 |
| AAV-PGC-1α | Regulator of oxidative phosphorylation; Regulator of mitochondrial biogenesis |
APP/PS1 | Improved learning and memory; Increase mitochondrial fusion protein (OPA1, MFN2); reduced mitochondrial fission protein (DRP1, FIS1) |
Wang et al., 2022 |
| AAV2-CEND1 | Neuronal lineage-specific modulator; Regulates mitochondrial dynamics via DRP1 |
5xFAD | Improved learning and memory; Increase mitochondrial fusion protein (OPA1, MFN2); reduced mitochondrial fission protein (DRP1) |
Xie et al., 2022 |
| AAV5-CHCHD6 | MICO complex component; Key component for mitochondrial crista formation |
APPNL−F-G KI AD | Reduced APP accumulation in the MAM; lowered C99 fragment; improved spatial working memory; restored synaptic function | Shang et al., 2022 |
| AAV9-MICU3 | Regulates mitochondrial calcium uptake | Tg-SwDI AD | Improved behavioral performance; enhance cerebral blood flow; reduce Aβ deposition | Zhou et al., 2023 |
| AAV2-PINK1 | Mitochondrial protein kinase; Mitophagy |
APPSwInd (J20) AD | Alleviated mitochondrial dysfunction and oxidative stress; increased ATP; Increased mitophagy; reduced Aβ accumulation |
Du et al., 2017 |
| AAV-MCL1 | OMM LIR motif receptor; Mitophagy; Regulates apoptosis |
APP/PS1 | Improved learning and memory; reduced hippocampal Aβ deposition; | Cen et al., 2020 |
| DISC1 | OMM LIR motif receptor; Mitophagy; Mitochondrial dynamics; |
APP/PS1 | Reduced expression of BACE1; reduced hippocampal Aβ deposition; improved learning and memory | Deng et al., 2016 |