Culling Less Fit Neurons Protects against Amyloid β-Induced Brain Damage and Cognitive and Motor Decline (Cell Reports 2018, 25:3661–3673)

報告日期: 2019/04/19
報告時間: 16:00/16:50
報告學生: 謝宗祺(以英文報告)
講評老師: 郭余民

Culling Less Fit Neurons Protects against Amyloid β-Induced

Brain Damage and Cognitive and Motor Decline

Coelho et al., 2018, Cell Reports 25, 3661–3673

Name: Hsieh, Tsung-Chi                                   Date: 2019/04/19

Commentator: Prof. Kuo, Yu-Min                            Place: Room 602

 Alzheimer’s disease (AD) is the most prevalent form of neurodegenerative disease, and it is characterized by progressive memory and cognitive impairments, behavior changes, and locomotor defect. According to the amyloid cascade hypothesis, the formation and aggregation of amyloid-β 42 peptide (Aβ42) is the primary cause of this disease. Furthermore, neuronal loss is also a pathological hallmark of AD; however, the role of it in the progression of AD is still unclear. By means of cell competition, multicellular organisms can maintain tissue homeostasis and remove the suboptimal cells to cope with developmental malformation, tumorigenesis, and aging. Eliminating the potentially dangerous cells on the basis of fitness status within a population of cells is called cell competition. This mechanism has not yet been well studied in the field of neurodegenerative disease, such as AD. The authors utilized Aβ42 transgenic fly, a Drosophila AD model, to investigate the potential role of fitness-based neuronal elimination in the onset and progression of disease. Drosophila translates the fitness status through fitness fingerprints which are encoded by three isoforms of flower protein: Flowerubi, FlowerLoseA, and FlowerLoseB. Flower is a conserved protein and the flower code is cell type specific. In neuronal system, the Flowerubi and FlowerLoseA are expressed ubiquitously, and FlowerLoseB are up-regulated in the less fit neurons. FlowerloseB targets the suboptimal neurons, and the initiation of downstream apoptosis requires the transcription of the fitness checkpoint gene azot. The authors found that the expression of Aβ42 peptide decreased the neuronal fitness encoded by flower and led to apoptosis executed by azot. Furthermore, such apoptosis has been indicated to delay Aβ42-induced brain damages, locomotor defect, and long-term memory impairment. Culling less fit neurons mediated by fitness comparison and apoptosis play a beneficial role in the progression of AD.


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