Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model

Lee, Banseok; Choi, Byoungyun; Park, Youngjae; Jang, Seokhui; Yuan, Chunyu; Lim, Chaejin; Lee, Jang Ho; Song, Gyun Jee; Cho, Kyoung Sang

doi:10.3390/ijms231911832

Cited by 4 publications

(3 citation statements)

References 82 publications

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“…Lee et al found that ZnT7 is important for neurodevelopment and that the knockdown of ZnT7 did not alter Aβ deposition but worsened neurodegeneration. These results suggest that proper distribution of zinc in the Golgi may be useful in protecting neurons and Alzheimer’s disease [ 54 ] ( Figure 5 ).…”

Section: Effect Of Golgi Stress On Neuropathiesmentioning

confidence: 99%

Emerging Evidence of Golgi Stress Signaling for Neuropathies

Shirai,

Yamauchi

2024

Neurology International

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The Golgi apparatus is an intracellular organelle that modifies cargo, which is transported extracellularly through the nucleus, endoplasmic reticulum, and plasma membrane in order. First, the general function of the Golgi is reviewed and, then, Golgi stress signaling is discussed. In addition to the six main Golgi signaling pathways, two pathways that have been increasingly reported in recent years are described in this review. The focus then shifts to neurological disorders, examining Golgi stress reported in major neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. The review also encompasses findings related to other diseases, including hypomyelinating leukodystrophy, frontotemporal spectrum disorder/amyotrophic lateral sclerosis, microcephaly, Wilson’s disease, and prion disease. Most of these neurological disorders cause Golgi fragmentation and Golgi stress. As a result, strong signals may act to induce apoptosis.

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Section: Effect Of Golgi Stress On Neuropathiesmentioning

confidence: 99%

Emerging Evidence of Golgi Stress Signaling for Neuropathies

Shirai,

Yamauchi

2024

Neurology International

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“…Their findings may provide a deeper understanding of the mechanisms through which the consumption of these alimentary products is related to the development of neuronal diseases. In the second paper, by using Drosophila , Lee et al demonstrated that ZnT86D, a Drosophila ortholog of zinc transporter ZnT7, plays an important role in the neurodevelopment and pathogenesis of AD [ 3 ]. RNAi silencing of ZnT86D in neurons induced abnormal neurogenesis and neuronal cell death that resulted in reduced survival rates, locomotor activity, and lifespan.…”

mentioning

confidence: 99%

“…RNAi silencing of ZnT86D in neurons induced abnormal neurogenesis and neuronal cell death that resulted in reduced survival rates, locomotor activity, and lifespan. Interestingly, neuron-specific knockdown of ZnT86D in the AD model fly enhanced apoptosis and neurodegeneration without alterations in the deposition of amyloid beta and susceptibility to oxidative stress [ 3 ]. Since ZnT7 is mainly localized in the Golgi apparatus and endoplasmic reticulum (ER), their findings suggest that proper distribution of zinc in the Golgi apparatus and ER is critical for neuronal development and neuroprotection.…”

mentioning

confidence: 99%

Role of Drosophila in Human Disease Research 3.0

Cotterill,

Yamaguchi

2023

IJMS

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Neuronal fatty acid-binding protein enhances autophagy and suppresses amyloid-β pathology in a Drosophila model of Alzheimer’s disease

Jang,

Choi,

Lim

et al. 2024

PLoS Genet

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Fatty acid-binding proteins (FABPs) are small cytoplasmic proteins involved in intracellular lipid transport and bind free fatty acids, cholesterol, and retinoids. FABP3, the major neuronal FABP in the adult brain, is upregulated in the CSF of patients with Alzheimer’s disease (AD). However, the precise role of neuronal FABPs in AD pathogenesis remains unclear. This study investigates the contribution of fabp, the Drosophila homolog of FABP3 and FABP7, to amyloid β (Aβ) pathology using a Drosophila model. Neuronal knockdown of fabp shortened the lifespan of flies and increased age-related protein aggregates in the brain. In an AD model, fabp knockdown in neurons increased Aβ accumulation and Aβ-induced neurodegeneration, whereas fabp overexpression ameliorated Aβ pathology. Notably, fabp overexpression stimulated autophagy, which was inhibited by the knockdown of Eip75B, the Drosophila homolog of the peroxisome proliferator-activated receptor (PPAR). The PPAR activator rosiglitazone restored autophagy impaired by fabp knockdown and reduced fabp knockdown-induced increased Aβ aggregation and cell death. Furthermore, knockdown of either fabp or Eip75B in the wing imaginal disc or adult fly brain reduced the expression of Atg6 and Atg8a. Additionally, treatment of the fabp knockdown AD model flies with polyunsaturated fatty acids, such as docosahexaenoic acid or linoleic acid, partially alleviated cell death in the developing eye, restored impaired autophagy flux, reduced Aβ aggregation, and attenuated Aβ-induced cell death. Our results suggest that Drosophila fabp plays an important role in maintaining protein homeostasis during aging and protects neurons from Aβ-induced cell death by enhancing autophagy through the PPAR pathway. These findings highlight the potential importance of neuronal FABP function in AD pathogenesis.

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Roles of ZnT86D in Neurodevelopment and Pathogenesis of Alzheimer Disease in a Drosophila melanogaster Model

Cited by 4 publications

References 82 publications

Emerging Evidence of Golgi Stress Signaling for Neuropathies

Emerging Evidence of Golgi Stress Signaling for Neuropathies

Role of Drosophila in Human Disease Research 3.0

Neuronal fatty acid-binding protein enhances autophagy and suppresses amyloid-β pathology in a Drosophila model of Alzheimer’s disease

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