Neuronal Autophagy Regulates Presynaptic Neurotransmission by Controlling the Axonal Endoplasmic Reticulum

Kuijpers, Marijn; Kochlamazashvili, Gaga; Stumpf, Alexander; Puchkov, Dmytro; Swaminathan, Aarti; Lucht, Max Thomas; Krause, Eberhard; Maritzen, Tanja; Schmitz, Dietmar; Haucke, Volker

doi:10.1016/j.neuron.2022.01.029

Cited by 5 publications

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“…Macroautophagy (to which we refer to as autophagy) can be activated in all relevant cell types of the CNS [ 125 ]. Neuron-specific knockout of the essential autophagy gene Atg5 results in increased excitatory neurotransmission [ 126 ]. Autophagy also contributes to synaptic remodeling, for instance in long-term synaptic depression induced by NMDAR activation [ 127 ].…”

Section: Hallmark 3: Recycling and Turnovermentioning

confidence: 99%

The missing hallmark of health: psychosocial adaptation

López-Otín,

Kroemer

2024

CST

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The eight biological hallmarks of health that we initially postulated (Cell. 2021 Jan 7;184(1):33-63) include features of spatial compartmentalization (integrity of barriers, containment of local perturbations), maintenance of homeostasis over time (recycling & turnover, integration of circuitries, rhythmic oscillations) and an array of adequate responses to stress (homeostatic resilience, hormetic regulation, repair & regeneration). These hallmarks affect all eight somatic strata of the human body (molecules, organelles, cells, supracellular units, organs, organ systems, systemic circuitries and meta-organism). Here we postulate that mental and socioeconomic factors must be added to this 8×8 matrix as an additional hallmark of health (“psychosocial adaptation”) and as an additional stratum (“psychosocial interactions”), hence building a 9×9 matrix. Potentially, perturbation of each of the somatic hallmarks and strata affects psychosocial factors and vice versa. Finally, we discuss the (patho)physiological bases of these interactions and their implications for mental health improvement.

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Section: Hallmark 3: Recycling and Turnovermentioning

confidence: 99%

The missing hallmark of health: psychosocial adaptation

López-Otín,

Kroemer

2024

CST

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“…The autophagosomes produced in the soma are less mobile and tend to aggregate [ 83 ]. Moreover, in healthy neurons, autophagy regulates axonal endoplasmic reticulum calcium storage to modulate neurotransmission in the brain [ 84 ]. Protein aggregates disrupt neuronal homeostasis, leading to toxicity associated with neurodegeneration.…”

Section: Function Of Autophagy In Neurological Disordersmentioning

confidence: 99%

The Multiple Roles of Autophagy in Neural Function and Diseases

Li,

Qin,

Sheng

2023

Neurosci. Bull.

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Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes, where proteins, lipids, and organelles are degraded and recycled. According to the way the cytoplasmic components are engulfed, autophagy can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy. Recently, many studies have found that autophagy plays an important role in neurological diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, neuronal excitotoxicity, and cerebral ischemia. Autophagy maintains cell homeostasis in the nervous system via degradation of misfolded proteins, elimination of damaged organelles, and regulation of apoptosis and inflammation. AMPK-mTOR, Beclin 1, TP53, endoplasmic reticulum stress, and other signal pathways are involved in the regulation of autophagy and can be used as potential therapeutic targets for neurological diseases. Here, we discuss the role, functions, and signal pathways of autophagy in neurological diseases, which will shed light on the pathogenic mechanisms of neurological diseases and suggest novel targets for therapies.

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“…Autophagy in microglia may project beyond such a backup role, becoming an important element of their immune functions 75 . So far, autophagy in the CNS has been studied in neurons, mainly in their axons, to show its role in neuronal transmission 11,18,19,76 . As we stated above, mechanisms of autophagy in microglia are less known—in fact, it is not clear whether microglial autophagy occurs with the involvement of the main proteins of canonical autophagy; 77 therefore, it is difficult to anticipate the consequences of blocking MA in microglia in the context of overall cellular autophagic response.…”

Section: Migraine‐related Effects May Impair Macroautophagy In and Fa...mentioning

confidence: 99%

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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Neuronal Autophagy Regulates Presynaptic Neurotransmission by Controlling the Axonal Endoplasmic Reticulum

Cited by 5 publications

References 0 publications

The missing hallmark of health: psychosocial adaptation

The missing hallmark of health: psychosocial adaptation

The Multiple Roles of Autophagy in Neural Function and Diseases

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

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