Storage and transport of labile iron is mediated by lysosomes in axons and dendrites of hippocampal neurons DOI Open Access

Aiyarin Kittilukkana,

Asunción Carmona, Andréa Somogyi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract Iron dyshomeostasis in neurons, involving iron accumulation and abnormal redox balance, is implicated neurodegeneration. In particular, labile iron, a highly reactive pool of intracellular plays prominent role iron-induced neurological damage. However, the mechanisms governing detoxification transport within neurons are not fully understood. This study investigates storage ferrous Fe(II) cultured primary rat hippocampal neurons. distribution was studied using live cell confocal microscopy with selective fluorescent dye, synchrotron X-ray fluorescence (SXRF) for total distribution. Fluorescent labelling axon initial segment lysosomes allowed to be correlated these subcellular compartments. The results show that stored somas, axons dendrites lysosomal transported retrogradely anterogradely along dendrites. addition, we have developed methodological workflow quantify relative neurites. method based on correlative imaging combined quantitative elemental mapping by SXRF. Quantitative analysis revealed after exposure, accounts small but significant percentage content These result suggest exposure Fe(II), mainly present non-reactive form while smaller fraction can axons.

Language: Английский

The role of iron transporters and regulators in Alzheimer’s disease and Parkinson’s disease: Pathophysiological insights and therapeutic prospects DOI Open Access
Siqi Tian, Bing Wang,

Yiqian Ding

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117419 - 117419

Published: Sept. 8, 2024

Language: Английский

Citations

6
Brain Glucose Hypometabolism and Brain Iron Accumulation as Therapeutic Targets for Alzheimer’s Disease and Other CNS Disorders DOI Creative Commons
Indira Y. Rao, Leah R. Hanson, William H. Frey

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 271 - 271

Published: Feb. 19, 2025

Two common mechanisms contributing to multiple neurological disorders, including Alzheimer's disease, are brain glucose hypometabolism (BGHM) and iron accumulation (BIA). Currently, BGHM BIA both widely acknowledged as biomarkers that aid in diagnosing CNS distinguishing between disorders with similar symptoms, tracking disease progression. Therapeutics targeting can be beneficial treating neurocognitive symptoms. This review addresses the evidence for therapeutic potential of disorders. Intranasal insulin, which is anti-inflammatory increases cell energy, intranasal deferoxamine, reduces oxidative damage inflammation, represent promising treatments these mechanisms. Both targets AD other

Language: Английский

Citations

0
The Role of Glia in Wilson’s Disease: Clinical, Neuroimaging, Neuropathological and Molecular Perspectives DOI Open Access
Grażyna Gromadzka, Anna Wilkaniec, Beata Tarnacka

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7545 - 7545

Published: July 9, 2024

Wilson's disease (WD) is inherited in an autosomal recessive manner and caused by pathogenic variants of the

Language: Английский

Citations

2
Targeting Iron Responsive Elements (IREs) of APP mRNA into Novel Therapeutics to Control the Translation of Amyloid-β Precursor Protein in Alzheimer’s Disease DOI Creative Commons
Mateen A. Khan

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1669 - 1669

Published: Dec. 11, 2024

The hallmark of Alzheimer’s disease (AD) is the buildup amyloid-β (Aβ), which produced when amyloid precursor protein (APP) misfolds and deposits as neurotoxic plaques in brain. A functional iron responsive element (IRE) RNA stem loop encoded by APP 5′-UTR may be a target for regulating production protein. Since modifying Aβ expression can give anti-amyloid efficacy protective brain balance, targeted regulation synthesis through modulation sequence function novel method prospective therapy disease. Numerous mRNA interference strategies 2D structure, even though messenger RNAs like tRNAs rRNAs fold into complex, three-dimensional structures, adding another level complexity. IRE family among few known 3D regulatory elements. This review seeks to describe structural aspects IREs transcripts, including that protein, are relevant neurodegenerative diseases, AD. mRNAs encoding proteins involved metabolism controlled this similar base sequences. Like ferritin their 5′-UTR, controls 5′-UTR. Iron misregulation (IRPs) also investigated contrasted using measurements levels tau production, Aβ, APP. development AD aided binding promotes aggregation. small chemical therapeutics control IRE-modulated increasingly thought RNAs. Thus, has important therapeutic implications targeting structures.

Language: Английский

Citations

2
Storage and transport of labile iron is mediated by lysosomes in axons and dendrites of hippocampal neurons DOI Open Access

Aiyarin Kittilukkana,

Asunción Carmona, Andréa Somogyi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract Iron dyshomeostasis in neurons, involving iron accumulation and abnormal redox balance, is implicated neurodegeneration. In particular, labile iron, a highly reactive pool of intracellular plays prominent role iron-induced neurological damage. However, the mechanisms governing detoxification transport within neurons are not fully understood. This study investigates storage ferrous Fe(II) cultured primary rat hippocampal neurons. distribution was studied using live cell confocal microscopy with selective fluorescent dye, synchrotron X-ray fluorescence (SXRF) for total distribution. Fluorescent labelling axon initial segment lysosomes allowed to be correlated these subcellular compartments. The results show that stored somas, axons dendrites lysosomal transported retrogradely anterogradely along dendrites. addition, we have developed methodological workflow quantify relative neurites. method based on correlative imaging combined quantitative elemental mapping by SXRF. Quantitative analysis revealed after exposure, accounts small but significant percentage content These result suggest exposure Fe(II), mainly present non-reactive form while smaller fraction can axons.

Language: Английский

Citations

0