Neuronal dysfunction with aging and its amelioration

Ando, Susumu

doi:10.2183/pjab.88.266

Cited by 12 publications

(11 citation statements)

References 76 publications

(120 reference statements)

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“…Changes in ganglioside composition with age also occur in liver [ 68 ]. There are only indications on the functional consequences of such changes [ 23 ].…”

Section: Occurrencementioning

confidence: 99%

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Ganglioside Biochemistry

2012

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“…Changes in ganglioside composition with age also occur in liver [ 68 ]. There are only indications on the functional consequences of such changes [ 23 ].…”

Section: Occurrencementioning

confidence: 99%

“… Structure of GQ1b, one of the most abundant gangliosides in adult human brain, which is involved in long term potentiation, synaptic plasticity, and improvement of cognitive function [ 23 ]. …”

Section: Figurementioning

confidence: 99%

Ganglioside Biochemistry

2012

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“…The present synaptophysin accumulations might also be linked to an increased synapse formation, which could be further enhanced by the increased number of neuronal processes resulting in an enlarged contact area of the DRG neurons. Similarly, previous studies demonstrated that gangliosides have an impact on the synaptic plasticity and function of rat hippocampal neurons and thereby influence long term potentiation and learning ability 107 . Formation and maintenance of synapses are dependent on various retrograde messengers including neurotrophins 108 .…”

mentioning

confidence: 60%

Neurotrophic effects of GM1 ganglioside, NGF, and FGF2 on canine dorsal root ganglia neurons in vitro

Schwarz¹,

Lehmbecker²,

Tongtako

et al. 2020

Sci Rep

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certain growth factors 23. Gangliosides are sialic acid-containing glycosphingolipids that can be found in different cellular membranes. In the CNS gangliosides account for up to 10% of the total lipid content in neurons 24. They are involved in intercellular communication, cellular differentiation, neuronal development, and regeneration 25-28 due to their capacity to modulate Ca 2+ influx and their influence on the function of receptors for muscarinic acetylcholine, serotonin, glutamine, neurotransmitters, and neurotrophic factors 29. Cellular gangliosides concentrate in lipid microdomains termed lipid rafts, which are signaling platforms rich in cholesterol and glycosphingolipids and contain amongst others high affinity tropomyosin-related kinase (Trk) and low affinity neurotrophin receptors (p75 NTR) 30-32. These receptors are activated by nerve growth factor (NGF) and other neurotrophic factors and have a strong impact on neuronal development, maintenance, and survival as well as memory formation and storage 33,34. Anti-G M1 antibodies modulate the membrane-associated sphingomyelin metabolism by altering neutral sphingomyelinase activity thereby inhibiting NGF action on rat pheochromocytoma (PC12) cells 35,36. G M1 and NGF protect primary cultured rat embryonic dorsal root ganglia (DRG) and spinal cord neurons from glutamate-induced excitotoxicity 37,38. Both molecules may function by modulating Ca 2+ homeostasis, maintaining normal mitochondrial membrane potential or by promoting the mRNA expression of neuronal proteins such as growth associated protein 43 and neurofilaments (NFs) 38,39. G M1 also protects rats against high altitude cerebral edema by suppressing oxidative stress and production of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α 40. Nevertheless, another study using an ischemia/reperfusion model in rats demonstrated that G M1 neuroprotection seems to be dependent on p75 NTR 41. Exogenous gangliosides also directly interact with growth factors such as basic fibroblast growth factor (FGF2) and inhibit FGF receptor binding 42,43. Moreover, G M1 can inhibit FGF2-mediated effects by acting on the same intracellular signaling molecules. For instance, FGF2 stimulates the activity of glycogen synthase kinase 3 (GSK3) in proliferating adult rat hippocampal progenitor cells, whereas G M1 prevents GSK3 activation in organotypic hippocampal slice cultures 44,45. In contrast, cell-associated G M1 has been described to act as a functional co-receptor for FGF2 43. Despite its name, FGF2 plays an essential role in neurogenesis, differentiation, axonal branching, and neuron survival in various types of brain and peripheral nerve lesions 46,47. FGF2 also stimulates the proliferation of neuronal precursor cells isolated from postnatal murine DRGs 48. The ability of adult rat ganglion cells to regrow axons in vitro can be influenced by FGF2 and G M1 49. Neurotrophic effects of FGF2 seem to be also mediated by soluble mediators released from glial cells 50. Summarized, NGF, FGF2 and gangliosides such as G M1 ...

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“…1,2 In aged conditions, many physical, biological, chemical, neurophysiological and neuropathological changes occur due to loss in synaptic plasticity, synaptic dysfunction, which further leads to subsequent triggering of neurodegenerative processes. 3 The growing need for the treatment of cognitive impairment due to aging or dementia has led to the search for potential cognition enhancing drugs. The various compounds presently under development represent an alternative to cholino-mimetic therapy and include new chemical entities as well as piracetam and its newer analogs.…”

Section: Introductionmentioning

confidence: 99%