a(GO:synapse)
It has been demonstrated that cholinergic synapses are particularly affected by Aβ oligomers early neurotoxicity [218, 219] and that synaptic loss is the major correlate of cognitive impairment PubMed:26813123
The explanation proposed by the authors is that alpha7 nAChR activation through nicotine binding could promote survival pathways and recover the synaptic damage caused by Abeta (Inestrosa et al., 2013) PubMed:25514383
The explanation proposed by the authors is that alpha7 nAChR activation through nicotine binding could promote survival pathways and recover the synaptic damage caused by Abeta (Inestrosa et al., 2013) PubMed:25514383
Dementia is a debilitating condition frequent in ageing populations, and Alzheimer's Disease (AD) accounts for 70% of all dementia cases. AD is characterized by neuropathological hallmarks consisting of an accumulation of Amyloid beta peptide (Ab) in extracellular plaques, intracellular deposits of tau protein, neuronal loss and, more recently, a prominent synaptic loss was identified (Braak and Braak,1991; Masliah et al., 2001; Selkoe,1991; Spires-Jones and Hyman, 2014) PubMed:25514383
This may be due to the strong Tau pathology of the toxic pro-aggregant TauRDΔK leading to Tau aggregation, loss of synapses and loss of neurons PubMed:29202785
These tau oligomers potentiate neuronal damage, leading to neurodegeneration and traumatic brain injury (Hawkins et al., 2013; Gerson et al., 2014a, 2016; Sengupta et al., 2015). Moreover, they have been implicated in synaptic loss as shown in studies of wild-type human tau transgenic mice (Spires et al., 2006; Berger et al., 2007; Clavaguera et al., 2013) PubMed:28420982
Overexpression of MARK4 led to tau hyperphosphorylation, reduced expression of synaptic markers, and loss of dendritic spines and synapses, phenotypes also observed after Aβ treatment. Importantly, expression of a non-phosphorylatable form of tau with the PAR-1/MARK site mutated blocked the synaptic toxicity induced by MARK4 overexpression or Aβ treatment. To probe the involvement of endogenous MARK kinases in mediating the synaptic toxicity of Aβ, we employed a peptide inhibitor capable of effectively and specifically inhibiting the activities of all PAR-1/MARK family members. This inhibitor abrogated the toxic effects of Aβ oligomers on dendritic spines and synapses as assayed at the morphological and electrophysiological levels. PubMed:22156579
p39, but not p35, is selectively upregulated by histone acetylation-mediated transcription, underlying the robust increase of Cdk5 activity during rat and mouse neuronal differentiation. Loss of p39 attenuates Cdk5 activity in neurons and preferentially affects phosphorylation of specific Cdk5 targets, leading to aberrant axonal growth and impaired dendritic spine and synapse formation. PubMed:27807169
In vivo use of phosphatase inhibitors such as okadaic acid has been shown in many studies to induce cognitive impairment and widespread neurotoxic effects that are reminiscent of the hallmark pathological processes occurring in AD pathology, i.e., the accumulation of P-tau, amyloidogenesis, synapse loss and neurodegeneration (Malchiodi-Albedi et al., 1997; Arendt et al., 1998; Sun et al.,2003; Kamat et al.,2013) PubMed:24653673
Moreover, administration of UCH-L1 can reverse the amyloid b-protein–induced synaptic dysfunction and memory loss in transgenic mice overexpressing APP and PS1 (Gong et al. 2006). PubMed:22908190
Among the various molecular species of Abeta present in the brain, soluble oligomeric forms of Abeta are arguably the most plausible candidates to impair synaptic function (reviewed in Walsh and Selkoe 2004). PubMed:22908190
Synaptic loss has long been documented in AD brain (Gonatas et al. 1967) and, as expected, is strongly correlated with the degree of cognitive impairment (Terry et al. 1991). PubMed:22908190
Pathological rab5 activation, which in Down syndrome is dependent on bCTF generation (Jiang et al. 2010), can up-regulate endocytosis in a manner functionally equivalent to the elevated endocytosis associated with increased synaptic activity, which is considered a source of Ab generation (Cirrito et al. 2008). PubMed:22908190
Similar therapeutic effects, including restoration of synaptic functions, are seen in APP mouse models after deleting cystatin C (Sun et al. 2008), by overexpressing cathepsin B (Mueller-Steiner et al. 2006), or by enhancing its activity (Butler et al. 2011). PubMed:22908190
Similar therapeutic effects, including restoration of synaptic functions, are seen in APP mouse models after deleting cystatin C (Sun et al. 2008), by overexpressing cathepsin B (Mueller-Steiner et al. 2006), or by enhancing its activity (Butler et al. 2011). PubMed:22908190
Moreover, administration of UCH-L1 can reverse the amyloid b-protein–induced synaptic dysfunction and memory loss in transgenic mice overexpressing APP and PS1 (Gong et al. 2006). PubMed:22908190
The earliest symptoms of AD are believed to be due to synaptic dysfunction, and in this context, numerous studies have established a significant role of the UPS in the regulation of synaptic plasticity. PubMed:22908190
Synaptic loss has long been documented in AD brain (Gonatas et al. 1967) and, as expected, is strongly correlated with the degree of cognitive impairment (Terry et al. 1991). PubMed:22908190
TauRDΔK comprises the structural elements required for the pathologic assembly of tau filaments, and it causes reversible memory deficits and synapse loss in regulatable transgenic mice [11,25]. PubMed:28528849
Tau oligomers from TauRDΔK and TauFLΔK mice reduced the density of the synapses by w50%, whereas tau from wild-type mice had no effect on the density (Fig. 7G). PubMed:28528849
Tau oligomers from TauRDΔK and TauFLΔK mice reduced the density of the synapses by w50%, whereas tau from wild-type mice had no effect on the density (Fig. 7G). PubMed:28528849
acr-14 controls body movement by modulating the synaptic inputs and outputs of the ventral cord neural circuitry (83). PubMed:29191965
One exception is the report of the accumulation of tau aggregates in presynaptic boutons in transgenic mice, whereby it induces synaptic dysfunction and loss of presynapses (77). PubMed:29191965
As a result, the proaggregant lines showed a range of defects including paralysis, axonal degeneration of GABAergic and cholinergic motor neurons, presynaptic defects, synapse loss, and mitochondrial transport defects early in adulthood PubMed:29191965
First, hyperphosphorylation of tau might induce tau missorting from axons to the somatodendritic compartment, which can cause synaptic dysfunction PubMed:26631930
Hyperphosphorylation, mutations and overexpression of tau can drive the mislocalization of tau into postsynaptic spines, resulting in synaptic dysfunction PubMed:26631930
Hyperphosphorylation, mutations and overexpression of tau can drive the mislocalization of tau into postsynaptic spines, resulting in synaptic dysfunction PubMed:26631930
Hyperphosphorylation, mutations and overexpression of tau can drive the mislocalization of tau into postsynaptic spines, resulting in synaptic dysfunction PubMed:26631930
Hyperphosphorylation, mutations and overexpression of tau can drive the mislocalization of tau into postsynaptic spines, resulting in synaptic dysfunction PubMed:26631930
Other species of NF-κB have not been found at the synapses suggesting that the synapses contain the p65-p50 heterodimer exclusively PubMed:28745240
This gene encodes for the DISC1 ubiquitous protein, which is implicated in neurogenesis, neuronal migration, axon/dendrite, and synapse formation PubMed:30061532
In schizophrenia, a progressive synaptic disorder is likely to promote neurodegeneration PubMed:30061532
Additionally, given that ADNP and NAP are linked with autophagy (13), cell adhesion (35), immune response (36), autism (6, 13, 15, 17, 27), and synapse-related processes (6), the analysis included several representative genes pertaining to these processes PubMed:30106381
Additionally, given that ADNP and NAP are linked with autophagy (13), cell adhesion (35), immune response (36), autism (6, 13, 15, 17, 27), and synapse-related processes (6), the analysis included several representative genes pertaining to these processes PubMed:30106381
It has been demonstrated that cholinergic synapses are particularly affected by Aβ oligomers early neurotoxicity [218, 219] and that synaptic loss is the major correlate of cognitive impairment PubMed:26813123
Dementia is a debilitating condition frequent in ageing populations, and Alzheimer's Disease (AD) accounts for 70% of all dementia cases. AD is characterized by neuropathological hallmarks consisting of an accumulation of Amyloid beta peptide (Ab) in extracellular plaques, intracellular deposits of tau protein, neuronal loss and, more recently, a prominent synaptic loss was identified (Braak and Braak,1991; Masliah et al., 2001; Selkoe,1991; Spires-Jones and Hyman, 2014) PubMed:25514383
At the cellular level, nAChRs can underlie synaptic responses, neuronal excitability, and neurotransmitter release (Dajas-Bailador and Wonnacott, 2004; Gotti and Clementi, 2004; Hogg et al., 2003) PubMed:28445721
p39, but not p35, is selectively upregulated by histone acetylation-mediated transcription, underlying the robust increase of Cdk5 activity during rat and mouse neuronal differentiation. Loss of p39 attenuates Cdk5 activity in neurons and preferentially affects phosphorylation of specific Cdk5 targets, leading to aberrant axonal growth and impaired dendritic spine and synapse formation. PubMed:27807169
Overexpression of MARK4 led to tau hyperphosphorylation, reduced expression of synaptic markers, and loss of dendritic spines and synapses, phenotypes also observed after Aβ treatment. Importantly, expression of a non-phosphorylatable form of tau with the PAR-1/MARK site mutated blocked the synaptic toxicity induced by MARK4 overexpression or Aβ treatment. To probe the involvement of endogenous MARK kinases in mediating the synaptic toxicity of Aβ, we employed a peptide inhibitor capable of effectively and specifically inhibiting the activities of all PAR-1/MARK family members. This inhibitor abrogated the toxic effects of Aβ oligomers on dendritic spines and synapses as assayed at the morphological and electrophysiological levels. PubMed:22156579
The earliest symptoms of AD are believed to be due to synaptic dysfunction, and in this context, numerous studies have established a significant role of the UPS in the regulation of synaptic plasticity. PubMed:22908190
Synaptic loss has long been documented in AD brain (Gonatas et al. 1967) and, as expected, is strongly correlated with the degree of cognitive impairment (Terry et al. 1991). PubMed:22908190
Synaptic loss has long been documented in AD brain (Gonatas et al. 1967) and, as expected, is strongly correlated with the degree of cognitive impairment (Terry et al. 1991). PubMed:22908190
In transgenic mouse models of AD, synaptic deficits have been detected prior to the formation of amyloid plaques (Hsia et al. 1999). PubMed:22908190
Pathological rab5 activation, which in Down syndrome is dependent on bCTF generation (Jiang et al. 2010), can up-regulate endocytosis in a manner functionally equivalent to the elevated endocytosis associated with increased synaptic activity, which is considered a source of Ab generation (Cirrito et al. 2008). PubMed:22908190
Similar therapeutic effects, including restoration of synaptic functions, are seen in APP mouse models after deleting cystatin C (Sun et al. 2008), by overexpressing cathepsin B (Mueller-Steiner et al. 2006), or by enhancing its activity (Butler et al. 2011). PubMed:22908190
To date, the physiological function of dendritic tau has not been well characterized. It may be involved in the regulation of synaptic plasticity, as pharmacological synaptic activation induces translocation of endogenous tau from the dendritic shaft to excitatory postsynaptic compartments in cultured mouse neurons and in acute hippocampal slices PubMed:26631930
Hyperphosphorylation, mutations and overexpression of tau can drive the mislocalization of tau into postsynaptic spines, resulting in synaptic dysfunction PubMed:26631930
Other species of NF-κB have not been found at the synapses suggesting that the synapses contain the p65-p50 heterodimer exclusively PubMed:28745240
In schizophrenia, a progressive synaptic disorder is likely to promote neurodegeneration PubMed:30061532
This gene encodes for the DISC1 ubiquitous protein, which is implicated in neurogenesis, neuronal migration, axon/dendrite, and synapse formation PubMed:30061532
Additionally, given that ADNP and NAP are linked with autophagy (13), cell adhesion (35), immune response (36), autism (6, 13, 15, 17, 27), and synapse-related processes (6), the analysis included several representative genes pertaining to these processes PubMed:30106381
Additionally, given that ADNP and NAP are linked with autophagy (13), cell adhesion (35), immune response (36), autism (6, 13, 15, 17, 27), and synapse-related processes (6), the analysis included several representative genes pertaining to these processes PubMed:30106381
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.