BACKGROUND: Alzheimer's disease (AD), an age-related progressive neurodegenerative disorder, exhibits reduced cognitive functions with no cure to date. One of the reasons for AD is the extracellular accumulation of Amyloid-beta 42 (Aβ42) plaques. Misexpression of human Aβ42 in the developing retina of Drosophila exhibits AD-like neuropathology. Accumulation of Aβ42 plaque(s) triggers aberrant signaling resulting in neuronal cell death by unknown mechanism(s). METHOD: Alzheimer's disease (AD), an age-related progressive neurodegenerative disorder, exhibits reduced cognitive functions with no cure to date. One of the reasons for AD is the extracellular accumulation of Amyloid-beta 42 (Aβ42) plaques. Misexpression of human Aβ42 in the developing retina of Drosophila exhibits AD-like neuropathology. Accumulation of Aβ42 plaque(s) triggers aberrant signaling resulting in neuronal cell death by unknown mechanism(s). RESULT: Gain-of-function of mir-277 rescues Aβ42 mediated neurodegeneration whereas loss-of-function of mir-277 enhances Aβ42 mediated neurodegeneration. Moreover, misexpression of higher levels of mir-277 in the GMR>Aβ42 background restores the retinal axonal targeting indicating functional rescue. Furthermore, we have identified head involution defective (hid) as one of the targets of mir-277. The hid transcript levels are decreased by one third when mir-277 is misexpressed in the GMR>Aβ42 background in comparison to the GMR>Aβ42 fly model. CONCLUSION: Hereby we provide a mechanism of how mir-277 modulates Aβ42 mediated neurodegeneration by regulating hid transcript levels and demonstrate its neuroprotective role in Aβ42-mediated neuropathology.
Date:
2021-12
Relation:
Alzheimer's and Dementia. 2021 Dec;17(Suppl. 2):Article number e058678.
