Brain-derived neurotrophic factor stimulates the retrograde pathway for axonal autophagy

Sidibe, David; Kulkarni, Vineet Vinay; Dong, Audrey; Herr, Jessica Brandt; Vogel, Maria C.; Stempel, Max Henry; Maday, Sandra

doi:10.1016/j.jbc.2022.102673

Cited by 7 publications

(7 citation statements)

References 72 publications

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“…BDNF may be involved in axonal autophagy as it was shown that it might induce autophagic flux in primary neurons by stimulating the retrograde pathway for autophagy in axons. 53 An increase in autophagosome density and retrograde flux in axons and a corresponding increase in autophagosome density in the soma were observed in that study; however, retrograde autophagosomes did not appear to carry active BDNF, suggesting that autophagosomes might not play a major role in relaying neurotrophic signaling information across the axon. Therefore, BDNFstimulated autophagy in axons may result from a need to degrade neuronal debris resulting from BDNF-induced processes.…”

Section: Neuron S' Interpl Ay With MI Crog Lia In Mig R Aine Pathog E...mentioning

confidence: 52%

“…Furthermore, P2X4R activation causes the adenosine triphosphate (ATP)‐mediated synthesis and release of BDNF through soluble N ‐ethylmaleimide‐sensitive‐factor attachment protein receptor –mediated exocytosis from microglia and hindering of P2X4R reduces that effect; 52 therefore, P2X4R can be involved in microglia‐mediated migraine pathogenesis underlined by the release of BDNF. BDNF may be involved in axonal autophagy as it was shown that it might induce autophagic flux in primary neurons by stimulating the retrograde pathway for autophagy in axons 53 . An increase in autophagosome density and retrograde flux in axons and a corresponding increase in autophagosome density in the soma were observed in that study; however, retrograde autophagosomes did not appear to carry active BDNF, suggesting that autophagosomes might not play a major role in relaying neurotrophic signaling information across the axon.…”

Section: Neurons’ Interplay With Microglia In Migraine Pathogenesismentioning

confidence: 61%

“…The involvement of BDNF in the regulation of neuronal autophagy was confirmed in a study with live-cell imaging in C57BL/6 mouse embryo primary neurons treated with exogenous BDNF. 53 That work showed that BDNF upregulates autophagic flux in primary neurons and stimulates retrograded transport of axonal autophagosomes; however, the great majority of axonal autophagosomes do not transport the BDNF cargo. Therefore, axonal autophagosomes may not carry BDNF-mediated neurotrophin signaling information.…”

Section: Mig R Aine-rel Ated E Vents Induce B Dnf-mediated Deg R Adat...mentioning

confidence: 99%

“…BDNF may stimulate neuronal autophagy for its canonical degradative functions. 53 An earlier study showed that BDNF might regulate neuronal plasticity through the regulation of autophagy. 91 That study showed that BDNF suppressed autophagy in in vitro neurons and in vivo in the mouse brain; however, those studies focused mainly on nutritional regulation of autophagy and neural plasticity as the main experiments supporting the final conclusion were performed in fasting and ad libitum conditions.…”

Section: Mig R Aine-rel Ated E Vents Induce B Dnf-mediated Deg R Adat...mentioning

confidence: 99%

“…The question is whether the changes caused by BDNF‐mediated autophagy can be related to migraine. BDNF may stimulate neuronal autophagy for its canonical degradative functions 53 …”

Section: Migraine‐related Events Induce Bdnf‐mediated Degradative Aut...mentioning

confidence: 99%

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Autophagy may protect the brain against prolonged consequences of headache attacks: A narrative/hypothesis review

Fila,

Pawlowska,

Szczepanska

et al. 2023

Headache

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ObjectiveTo assess the potential of autophagy in migraine pathogenesis.BackgroundThe interplay between neurons and microglial cells is important in migraine pathogenesis. Migraine‐related effects, such as cortical spreading depolarization and release of calcitonin gene–related peptide, may initiate adenosine triphosphate (ATP)‐mediating pro‐nociceptive signaling in the meninges causing headaches. Such signaling may be induced by the interaction of ATP with purinergic receptor P2X 7 (P2X7R) on microglial cells leading to a Ca2+‐mediated pH increase in lysosomes and release of autolysosome‐like vehicles from microglial cells indicating autophagy impairment.MethodsA search in PubMed was conducted with the use of the terms “migraine,” “autophagy,” “microglia,” and “degradation” in different combinations.ResultsImpaired autophagy in microglia may activate secretory autophagy and release of specific proteins, including brain‐derived neurotrophic factor (BDNF), which can be also released through the pores induced by P2X7R activation in microglial cells. BDNF may be likewise released from microglial cells upon ATP‐ and Ca2+‐mediated activation of another purinergic receptor, P2X4R. BDNF released from microglia might induce autophagy in neurons to clear cellular debris produced by oxidative stress, which is induced in the brain as the response to migraine‐related energy deficit. Therefore, migraine‐related signaling may impair degradative autophagy, stimulate secretory autophagy in microglia, and degradative autophagy in neurons. These effects are mediated by purinergic receptors P2X4R and P2X7R, BDNF, ATP, and Ca2+.ConclusionDifferent effects of migraine‐related events on degradative autophagy in microglia and neurons may prevent prolonged changes in the brain related to headache attacks.

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Section: Neuron S' Interpl Ay With MI Crog Lia In Mig R Aine Pathog E...mentioning

confidence: 52%

Section: Neurons’ Interplay With Microglia In Migraine Pathogenesismentioning

confidence: 61%

Section: Mig R Aine-rel Ated E Vents Induce B Dnf-mediated Deg R Adat...mentioning

confidence: 99%

Section: Mig R Aine-rel Ated E Vents Induce B Dnf-mediated Deg R Adat...mentioning

confidence: 99%

“…The question is whether the changes caused by BDNF‐mediated autophagy can be related to migraine. BDNF may stimulate neuronal autophagy for its canonical degradative functions 53 …”

Section: Migraine‐related Events Induce Bdnf‐mediated Degradative Aut...mentioning

confidence: 99%

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Autophagy may protect the brain against prolonged consequences of headache attacks: A narrative/hypothesis review

Fila,

Pawlowska,

Szczepanska

et al. 2023

Headache

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Autophagy initiation triggers p150Glued–AP-2β interaction on the lysosomes and facilitates their transport

Tempes,

Bogusz,

Brzozowska

et al. 2024

Cell. Mol. Life Sci.

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The endocytic adaptor protein 2 (AP-2) complex binds dynactin as part of its noncanonical function, which is necessary for dynein-driven autophagosome transport along microtubules in neuronal axons. The absence of this AP-2-dependent transport causes neuronal morphology simplification and neurodegeneration. The mechanisms that lead to formation of the AP-2-dynactin complex have not been studied to date. However, the inhibition of mammalian/mechanistic target of rapamycin complex 1 (mTORC1) enhances the transport of newly formed autophagosomes by influencing the biogenesis and protein interactions of Rab-interacting lysosomal protein (RILP), another dynein cargo adaptor. We tested effects of mTORC1 inhibition on interactions between the AP-2 and dynactin complexes, with a focus on their two essential subunits, AP-2β and p150Glued. We found that the mTORC1 inhibitor rapamycin enhanced p150Glued–AP-2β complex formation in both neurons and non-neuronal cells. Additional analysis revealed that the p150Glued–AP-2β interaction was indirect and required integrity of the dynactin complex. In non-neuronal cells rapamycin-driven enhancement of the p150Glued–AP-2β interaction also required the presence of cytoplasmic linker protein 170 (CLIP-170), the activation of autophagy, and an undisturbed endolysosomal system. The rapamycin-dependent p150Glued–AP-2β interaction occurred on lysosomal-associated membrane protein 1 (Lamp-1)-positive organelles but without the need for autolysosome formation. Rapamycin treatment also increased the acidification and number of acidic organelles and increased speed of the long-distance retrograde movement of Lamp-1-positive organelles. Altogether, our results indicate that autophagy regulates the p150Glued–AP-2β interaction, possibly to coordinate sufficient motor-adaptor complex availability for effective lysosome transport.

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Structural Mechanisms of Mitochondrial Quality Control Mediated by PINK1 and Parkin

Trempe

Gehring

2023

Journal of Molecular Biology

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Brain-derived neurotrophic factor stimulates the retrograde pathway for axonal autophagy

Cited by 7 publications

References 72 publications

Autophagy may protect the brain against prolonged consequences of headache attacks: A narrative/hypothesis review

Autophagy may protect the brain against prolonged consequences of headache attacks: A narrative/hypothesis review

Autophagy initiation triggers p150Glued–AP-2β interaction on the lysosomes and facilitates their transport

Structural Mechanisms of Mitochondrial Quality Control Mediated by PINK1 and Parkin

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