Diverse cellular and molecular modes of axon degeneration

Neukomm, Lukas J.; Freeman, Marc

doi:10.1016/j.tcb.2014.04.003

Cited by 121 publications

(127 citation statements)

References 86 publications

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“…Furthermore, in flies overexpressing the causal gene product of the slow Wallerian degeneration mouse in C4da neurons, dendrite pruning was slightly but significantly retarded 15,44 . It is thus of interest to examine that the local activation of the Rab5-and dynamin-dependent endocytosis might be involved in the progress of large-scale axon degeneration in pathological conditions in the mammalian nervous system 45,46 . Further studies on the role of local endocytosis in dendrite pruning should also help to elucidate molecular and cellular mechanisms underlying axon/dendrite degeneration in the developing nervous system.…”

Section: Discussionmentioning

confidence: 99%

Local endocytosis triggers dendritic thinning and pruning in Drosophila sensory neurons

et al. 2015

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The refinement of neural circuits involves dendrite pruning, a process that removes inappropriate projections that are formed during development. In Drosophila sensory neurons, compartmentalized calcium (Ca 2 þ ) transients in dendrites act as spatiotemporal cues to trigger pruning, yet how neurons define the dendrites with Ca 2 þ transients remains elusive. Here we report that local elevation of endocytic activity contributes to defining dendrites that generate Ca 2 þ transients, triggering pruning. In vivo imaging of single dendrites reveals an increase of endocytosis in proximal dendrites that spatially and temporally correlates with dendrite thinning, an early step in pruning tightly coupled with compartmentalized Ca 2 þ transients. Two GTPases, Rab5 and dynamin, are required for both the increased endocytic activity and compartmentalized Ca 2 þ transients. Further genetic analyses suggest that local endocytosis in proximal dendrites functions cooperatively with global endocytosis-mediated protein degradation pathways to promote dendrite pruning.

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Section: Discussionmentioning

confidence: 99%

Local endocytosis triggers dendritic thinning and pruning in Drosophila sensory neurons

et al. 2015

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“…There is evidence suggesting that nsDAn surviving the SN degeneration may present a partial loss of their phenotypic characteristics in the PD (Kastner et al ., 1993; Miller et al ., 1999; Gonzalez-Hernandez et al ., 2001, 2004; Chu et al ., 2006), a fact that could explain why a portion of the melanin-positive SN neurons does not express TH or other dopaminergic markers in PD (Kordower et al ., 2013). DAn degeneration probably begins in the distal axon and proceeds retrogradely (dying-back process) (Galvin et al ., 1999; Cheng et al ., 2010), inducing an early inhibition of the fast axonal transport (Coleman, 2005; Morfini et al ., 2007; De Vos et al ., 2008; Neukomm & Freeman, 2014) accompanied by a decreased expression of the dopaminergic phenotype (Bellinger et al ., 2011; Cheng et al ., 2011). A similar decrease in the dopaminergic phenotype has been found in the snDAn which survive to a partial degeneration of the nigrostriatal system (which may change its DAergic phenotype by a GABAergic phenotype) (Rodriguez & Gonzalez-Hernandez, 1999; Gonzalez-Hernandez et al ., 2001), and in nigrostriatal cells of animals with a degeneration of the contralateral snDAn (Gonzalez-Hernandez et al ., 2004).…”

Section: Physiological Changes Of Dan In Pd and Agingmentioning

confidence: 99%

Parkinson's disease as a result of aging

et al. 2015

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It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider phenomenon affecting cells all over the body, whereas Parkinson's disease seems to be restricted to certain brain centers and cell populations. However, reviewed data suggest that Parkinson's disease may be a local expression of aging on cell populations which, by their characteristics (high number of synaptic terminals and mitochondria, unmyelinated axons, etc.), are highly vulnerable to the agents promoting aging. The development of new knowledge about Parkinson's disease could be accelerated if the research on aging and Parkinson's disease were planned together, and the perspective provided by gerontology gains relevance in this field.

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“…While caspase activity has been traditionally assumed as a hallmark of apoptosis, growing studies reveal that non-apoptotic caspase activity plays potential roles in diverse normal cell functions, such as regulation of neuronal activity 79,80 , learning and memory 81,82,83,84 , suppression of necroptotic cell death 85,86 , spermatid individualization 87,88 , microRNA processing 89 , cell proliferation 90 , and cell fate patterning 91 . In addition to apoptosis and anastasis, the CaspaseTracker biosensor system can therefore detect non-apoptotic caspase activity, which is present in the brain and optic lobes, cardia, gut, Malpighian tubules, trachea, muscles, and other tissues of Drosophila 19,46,64 .…”

Section: Discussionmentioning

confidence: 99%

Detecting Anastasis <em>In Vivo</em> by CaspaseTracker Biosensor

Tang

Fung

Tang

2018

JoVE

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Anastasis (Greek for “rising to life”) is a recently discovered cell recovery phenomenon whereby dying cells can reverse late-stage cell death processes that are generally assumed to be intrinsically irreversible. Promoting anastasis could in principle rescue or preserve injured cells that are difficult to replace such as cardiomyocytes or neurons, thereby facilitating tissue recovery. Conversely, suppressing anastasis in cancer cells, undergoing apoptosis after anti-cancer therapies, may ensure cancer cell death and reduce the chances of recurrence. However, these studies have been hampered by the lack of tools for tracking the fate of cells that undergo anastasis in live animals. The challenge is to identify the cells that have reversed the cell death process despite their morphologically normal appearance after recovery. To overcome this difficulty, we have developed Drosophila and mammalian CaspaseTracker biosensor systems that can identify and permanently track the anastatic cells in vitro or in vivo. Here, we present in vivo protocols for the generation and use of the CaspaseTracker dual biosensor system to detect and track anastasis in Drosophila melanogaster after transient exposure to cell death stimuli. While conventional biosensors and protocols can label cells actively undergoing apoptotic cell death, the CaspaseTracker biosensor can permanently label cells that have recovered after caspase activation - a hallmark of late-stage apoptosis, and simultaneously identify active apoptotic processes. This biosensor can also track the recovery of the cells that attempted other forms of cell death that directly or indirectly involved caspase activity. Therefore, this protocol enables us to continuously track the fate of these cells and their progeny, facilitating future studies of the biological functions, molecular mechanisms, physiological and pathological consequences, and therapeutic implications of anastasis. We also discuss the appropriate controls to distinguish cells that undergo anastasis from those that display non-apoptotic caspase activity in vivo.

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Diverse cellular and molecular modes of axon degeneration

Cited by 121 publications

References 86 publications

Local endocytosis triggers dendritic thinning and pruning in Drosophila sensory neurons

Local endocytosis triggers dendritic thinning and pruning in Drosophila sensory neurons

Parkinson's disease as a result of aging

Detecting Anastasis <em>In Vivo</em> by CaspaseTracker Biosensor

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