Interneurons secrete prosaposin, a neurotrophic factor, to attenuate kainic acid-induced neurotoxicity

Nabeka, Hiroaki; Saito, Shouichiro; Li, Xuan; Shimokawa, Tetsuya; Khan, Md. Sakirul Islam; Yamamiya, Kimiko; Kawabe, Soichiro; Doihara, Takuya; Hamada, Fumihiko; Kobayashi, Naoto; Matsuda, Seiji

doi:10.1016/j.ibror.2017.07.001

Cited by 14 publications

(13 citation statements)

References 68 publications

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“…PSAP is suggested to be an essential neurotrophic factor since its secretion stimulates proliferation and maturation of immature neurons in the hippocampus DG, as well as provides protection against apoptosis. It was reported that deficiency of PSAP precedes massive neuronal loss in neurotoxic environments (Morishita et al, 2014 ; Nabeka et al, 2017 ).…”

Section: Focus On Msc-derived Exosomes and Their Role In Neuroplasticmentioning

confidence: 99%

Potential Effects of MSC-Derived Exosomes in Neuroplasticity in Alzheimer’s Disease

Reza-Zaldívar

Hernández-Sapiéns

Minjarez

et al. 2018

Front. Cell. Neurosci.

135

103

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Alzheimer’s disease (AD) is the most common type of dementia affecting regions of the central nervous system that exhibit synaptic plasticity and are involved in higher brain functions such as learning and memory. AD is characterized by progressive cognitive dysfunction, memory loss and behavioral disturbances of synaptic plasticity and energy metabolism. Cell therapy has emerged as an alternative treatment of AD. The use of adult stem cells, such as neural stem cells and Mesenchymal Stem Cells (MSCs) from bone marrow and adipose tissue, have the potential to decrease cognitive deficits, possibly by reducing neuronal loss through blocking apoptosis, increasing neurogenesis, synaptogenesis and angiogenesis. These processes are mediated primarily by the secretion of many growth factors, anti-inflammatory proteins, membrane receptors, microRNAs (miRNA) and exosomes. Exosomes encapsulate and transfer several functional molecules like proteins, lipids and regulatory RNA which can modify cell metabolism. In the proteomic characterization of the content of MSC-derived exosomes, more than 730 proteins have been identified, some of which are specific cell type markers and others are involved in the regulation of binding and fusion of exosomes with adjacent cells. Furthermore, some factors were found that promote the recruitment, proliferation and differentiation of other cells like neural stem cells. Moreover, within exosomal cargo, a wide range of miRNAs were found, which can control functions related to neural remodeling as well as angiogenic and neurogenic processes. Taking this into consideration, the use of exosomes could be part of a strategy to promote neuroplasticity, improve cognitive impairment and neural replacement in AD. In this review, we describe how exosomes are involved in AD pathology and discuss the therapeutic potential of MSC-derived exosomes mediated by miRNA and protein cargo.

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Section: Focus On Msc-derived Exosomes and Their Role In Neuroplasticmentioning

confidence: 99%

Potential Effects of MSC-Derived Exosomes in Neuroplasticity in Alzheimer’s Disease

Reza-Zaldívar

Hernández-Sapiéns

Minjarez

et al. 2018

Front. Cell. Neurosci.

135

103

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“…Prosaposin (PSAP) is also a lysosomal regulatory protein with significant neuroprotective properties [36–38]. Recent studies have shown biochemical interactions between PGRN and PSAP, with these interactions affecting the trafficking of these proteins to lysosomes [39–41].…”

Section: Introductionmentioning

confidence: 99%

“…PSAP deficiencies in mice led to significant impairment of PGRN trafficking to lysosomes but increased circulating levels of PGRN [41]. Experimental models of neuronal injury resulted in increased levels of PSAP in neurons and microglia [38, 42, 43]. The interactions of PGRN and PSAP are complex as both PSAP reduction and overexpression resulted in elevated levels of extracellular/secreted PGRN in different cellular models [4].…”

Section: Introductionmentioning

confidence: 99%

Characterization of lysosomal proteins Progranulin and Prosaposin and their interactions in Alzheimer’s disease and aged brains: increased levels correlate with neuropathology

Mendsaikhan

Tooyama

Bellier

et al. 2019

acta neuropathol commun

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Progranulin (PGRN) is a protein encoded by the GRN gene with multiple identified functions including as a neurotrophic factor, tumorigenic growth factor, anti-inflammatory cytokine and regulator of lysosomal function. A single mutation in the human GRN gene resulting in reduced PGRN expression causes types of frontotemporal lobar degeneration resulting in frontotemporal dementia. Prosaposin (PSAP) is also a multifunctional neuroprotective secreted protein and regulator of lysosomal function. Interactions of PGRN and PSAP affect their functional properties. Their roles in Alzheimer’s disease (AD), the leading cause of dementia, have not been defined. In this report, we examined in detail the cellular expression of PGRN in middle temporal gyrus samples of a series of human brain cases (n = 45) staged for increasing plaque pathology. Immunohistochemistry showed PGRN expression in cortical neurons, microglia, cerebral vessels and amyloid beta (Aβ) plaques, while PSAP expression was mainly detected in neurons and Aβ plaques, and to a limited extent in astrocytes. We showed that there were increased levels of PGRN protein in AD cases and corresponding increased levels of PSAP. Levels of PGRN and PSAP protein positively correlated with amyloid beta (Aβ), with PGRN levels correlating with phosphorylated tau (serine 205) levels in these samples. Although PGRN colocalized with lysosomal-associated membrane protein-1 in neurons, most PGRN associated with Aβ plaques did not. Aβ plaques with PGRN and PSAP deposits were identified in the low plaque non-demented cases suggesting this was an early event in plaque formation. We did not observe PGRN-positive neurofibrillary tangles. Co-immunoprecipitation studies of PGRN from brain samples identified only PSAP associated with PGRN, not sortilin or other known PGRN-binding proteins, under conditions used. Most PGRN associated with Aβ plaques were immunoreactive for PSAP showing a high degree of colocalization of these proteins that did not change between disease groups. As PGRN supplementation has been considered as a therapeutic approach for AD, the possible involvement of PGRN and PSAP interactions in AD pathology needs to be further considered.

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“…The presence of fewer injured neurons and more healthy neurons in the PS18-injected rats indicated that PS18 rescues CA1 neurons from KA-induced degeneration. The detection of higher levels of PSAP in PV-positive GABAergic inhibitory interneurons and their axons around pyramidal neurons suggested the axonal transport of PSAP [24,25] (Figure 1h-i). Similarly, PSAP was strongly expressed in the Purkinje cells and interneurons of the cerebellum of KA-injected rats [26].…”

Section: Psap Rescues Neurons From Damage Induced By Neurotoxic Agentsmentioning

confidence: 95%

Antimicrobial Properties of Plants of Chungtia Village Used Customarily to Treat Skin Related Ailments: From Antimicrobial Screening to Isolation of Active Compounds

Malewska

Kichu

Barnes

et al. 2018

AOICS

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Prosaposin (PSAP) is both a precursor protein of saposin A-D and a neuroprotective factor. In response to neuropathological disorders such as ischemia, neurotoxins, and nerve transection, PSAP is up-regulated such that both PSAP immunoreactivity and PSAP mRNA levels in neurons increase significantly. PSAP and an 18-mer peptide (PS18) derived from its neurotrophic region were shown to significantly protect damaged neurons. Meyer et al. [1] characterized the PSAP receptors GPR37 and GPR37L1, both of which are involved in neuronal protection, although their expression and their interactions with PSAP have not been fully elucidated (see the review of Smith [2]). However, the increased expression of PSAP and its receptors in damaged neurons and the surrounding glia points to a role for these proteins in protecting damaged cells in the nervous system. This mini-review examines the neuro-and glio-protective functions of PSAP and its receptors, based mainly on data from neuropathological in vivo models. Additional information can be found in the review by Meyer et al. [3].

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Interneurons secrete prosaposin, a neurotrophic factor, to attenuate kainic acid-induced neurotoxicity

Cited by 14 publications

References 68 publications

Potential Effects of MSC-Derived Exosomes in Neuroplasticity in Alzheimer’s Disease

Potential Effects of MSC-Derived Exosomes in Neuroplasticity in Alzheimer’s Disease

Characterization of lysosomal proteins Progranulin and Prosaposin and their interactions in Alzheimer’s disease and aged brains: increased levels correlate with neuropathology

Antimicrobial Properties of Plants of Chungtia Village Used Customarily to Treat Skin Related Ailments: From Antimicrobial Screening to Isolation of Active Compounds

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