Dysregulation of the progranulin-driven autophagy-lysosomal pathway mediates secretion of the nuclear protein TDP-43

Tanaka, Yoshinori; Ito, Shun-ichi; Honma, Yuki; Hasegawa, Masato; Kametani, Fuyuki; Suzuki, Genjiro; Kozuma, Lina; Takeya, Kosuke; Eto, Masumi

doi:10.1016/j.jbc.2023.105272

Cited by 4 publications

(9 citation statements)

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“…Another aspect of ALS pathology is proteinopathy, which involves the aggregation of Tdp-43 in the brain . Tdp-43 is secreted through EVs for intercellular transport, a phenomenon recently identified as regulated by the progranulin-driven autophagy . Though the finding requires direct validation in ALS mouse models, it does indicate toward EV as a contributor and potential target for ALS-associated proteinopathy.…”

Section: Role Of Evs In Brain Disorders: Involvement In Pathogenesis ...mentioning

confidence: 99%

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

Onkar,

Khan,

Goenka

et al. 2024

ACS Appl. Mater. Interfaces

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Information exchange is essential for the brain, where it communicates the physiological and pathological signals to the periphery and vice versa. Extracellular vesicles (EVs) are a heterogeneous group of membrane-bound cellular informants actively transferring informative calls to and from the brain via lipids, proteins, and nucleic acid cargos. In recent years, EVs have also been widely used to understand brain function, given their "cell-like" properties. On the one hand, the presence of neuron and astrocyte-derived EVs in biological fluids have been exploited as biomarkers to understand the mechanisms and progression of multiple neurological disorders; on the other, EVs have been used in designing targeted therapies due to their potential to cross the blood-brain-barrier (BBB). Despite the expanding literature on EVs in the context of central nervous system (CNS) physiology and related disorders, a comprehensive compilation of the existing knowledge still needs to be made available. In the current review, we provide a detailed insight into the multifaceted role of brain-derived extracellular vesicles (BDEVs) in the intricate regulation of brain physiology. Our focus extends to the significance of these EVs in a spectrum of disorders, including brain tumors, neurodegenerative conditions, neuropsychiatric diseases, autoimmune disorders, and others. Throughout the review, parallels are drawn for using EVs as biomarkers for various disorders, evaluating their utility in early detection and monitoring. Additionally, we discuss the promising prospects of utilizing EVs in targeted therapy while acknowledging the existing limitations and challenges associated with their applications in clinical scenarios. A foundational comprehension of the current state-of-the-art in EV research is essential for informing the design of future studies.

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Section: Role Of Evs In Brain Disorders: Involvement In Pathogenesis ...mentioning

confidence: 99%

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

Onkar,

Khan,

Goenka

et al. 2024

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

show abstract

“…SH-SY5Y cells stably expressing mRFP-LC3-GFP-LC3ΔG, ATG16L1 knockout HeLa cells, and control HeLa cells [ 12 ] were kindly gifted by David Rubinsztein's Lab (Cambridge, UK). SH-SY5Y and HeLa cells were cultured as previously reported [ 13 ].…”

Section: Methodsmentioning

confidence: 99%

“…An autolysosome analysis using SH-SY5Y cell stably expressing mCherry-LC3 and LAMP1-GFP was performed as previously reported [ 13 ]. Briefly, SH-SY5Y cells stably expressing mCherry-LC3 and LAMP1-GFP were seeded at a density of 1.0 × 10 4 cells on μ-Slide 8 Well high (ibidi).…”

Section: Methodsmentioning

confidence: 99%

“…An autolysosome analysis with DALGreen (DALG) staining was performed as previously reported [ 13 ]. Briefly, HeLa cells were seeded at a density of 1.0 × 10 4 cells on μ-Slide 8 Well high (ibidi).…”

Section: Methodsmentioning

confidence: 99%

“…An immunoblot analysis was conducted as described in a previous study [ 13 ]. Cells were lysed for 20 min with 1% (w/v) Sarkosyl in A68 [10 mM Tris-HCl buffer, pH 7.5, 0.8 M NaCl, 1 mM ethylene glycol bis(β-aminoethyl ether) -N,N,N,N -tetraacetic acid (EGTA)] on ice.…”

Section: Methodsmentioning

confidence: 99%

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