Intracellular accumulation of tau oligomers in astrocytes and their synaptotoxic action rely on Amyloid Precursor Protein Intracellular Domain-dependent expression of Glypican-4

Puliatti, Giulia; Puma, Domenica Donatella Li; Aceto, Giuseppe; Lazzarino, Giacomo; Acquarone, Erica; Mangione, Renata; D’Adamio, Luciano; Ripoli, Cristian; Arancio, Ottavio; Piacentini, Roberto; Grassi, Claudio

doi:10.1016/j.pneurobio.2023.102482

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…Specifically, AICD/AID enters the nucleus, where it binds to the promoter of gpc4 , enhancing expression of the GPC4 receptor at the membrane. Subsequently, GPC4 facilitates the internalization of extracellular oTau to the astrocytes [ 178 ], corroborating previous findings showing that GPC4 facilitates Aβ uptake from neuronal stem cells [ 179 ]. Of note, a reduction in GPC4 expression was observed in the brains of APP-KO mice or APP-TA mice in which the T668 site cannot be phosphorylated, underscoring the importance of T688 phosphorylation in AICD/AID production and eventually oTau internalization [ 178 ].…”

Section: Re-evaluating the Role Of App In Adsupporting

confidence: 88%

“…This could happen either by altering the signaling pathways mediated by AICD/AID or by post-translational changes in the APP. It was recently shown that APP-mediated expression of the heparan sulfate proteoglycan (HSPG), glypican 4 (GPC4), facilitates entry of oTau in astrocytes [ 178 ]. Specifically, AICD/AID enters the nucleus, where it binds to the promoter of gpc4 , enhancing expression of the GPC4 receptor at the membrane.…”

Section: Re-evaluating the Role Of App In Admentioning

confidence: 99%

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Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach

Haut,

Argyrousi,

Arancio

2023

IJMS

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After several years of research in the field of Alzheimer’s disease (AD), it is still unclear how amyloid-beta (Aβ) and Tau, two key hallmarks of the disease, mediate the neuropathogenic events that lead to AD. Current data challenge the “Amyloid Cascade Hypothesis” that has prevailed in the field of AD, stating that Aβ precedes and triggers Tau pathology that will eventually become the toxic entity in the progression of the disease. This perspective also led the field of therapeutic approaches towards the development of strategies that target Aβ or Tau. In the present review, we discuss recent literature regarding the neurotoxic role of both Aβ and Tau in AD, as well as their physiological function in the healthy brain. Consequently, we present studies suggesting that Aβ and Tau act independently of each other in mediating neurotoxicity in AD, thereafter, re-evaluating the “Amyloid Cascade Hypothesis” that places Tau pathology downstream of Aβ. More recent studies have confirmed that both Aβ and Tau could propagate the disease and induce synaptic and memory impairments via the amyloid precursor protein (APP). This finding is not only interesting from a mechanistic point of view since it provides better insights into the AD pathogenesis but also from a therapeutic point of view since it renders APP a common downstream effector for both Aβ and Tau. Subsequently, therapeutic strategies that act on APP might provide a more viable and physiologically relevant approach for targeting AD.

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Section: Re-evaluating the Role Of App In Adsupporting

confidence: 88%

Section: Re-evaluating the Role Of App In Admentioning

confidence: 99%

Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach

Haut,

Argyrousi,

Arancio

2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hyperphosphorylation of Tau is directly mediated by GPC4 via interaction with apolipoprotein E4 (APOE4) promoting the development of tauopathies, including AD (Saroja et al., 2022). Internalization and accumulation of tau oligomers by astrocytes involves GPC4 interactions with APP and has toxic effects altering gliotransmitter secretion negatively impacting on neuronal synaptic function (Puliatti et al., 2023). GPC1 is highly expressed in glioblastoma and has been suggested as a tumor biomarker (Listik & Toma, 2020).…”

Section: The Cell‐associated Proteoglycans Of the Cns/pnsmentioning

confidence: 99%

CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity

Melrose

2024

J of Neuroscience Research

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Central and peripheral nervous system (CNS/PNS) proteoglycans (PGs) have diverse functional roles, this study examined how these control cellular behavior and tissue function. The CNS/PNS extracellular matrix (ECM) is a dynamic, responsive, highly interactive, space‐filling, cell supportive, stabilizing structure maintaining tissue compartments, ionic microenvironments, and microgradients that regulate neuronal activity and maintain the neuron in an optimal ionic microenvironment. The CNS/PNS contains a high glycosaminoglycan content (60% hyaluronan, HA) and a diverse range of stabilizing PGs. Immobilization of HA in brain tissues by HA interactive hyalectan PGs preserves tissue hydration and neuronal activity, a paucity of HA in brain tissues results in a pro‐convulsant epileptic phenotype. Diverse CS, KS, and HSPGs stabilize the blood–brain barrier and neurovascular unit, provide smart gel neurotransmitter neuron vesicle storage and delivery, organize the neuromuscular junction basement membrane, and provide motor neuron synaptic plasticity, and photoreceptor and neuron synaptic functions. PG‐HA networks maintain ionic fluxes and microgradients and tissue compartments that contribute to membrane polarization dynamics essential to neuronal activation and neurotransduction. Hyalectans form neuroprotective perineuronal nets contributing to synaptic plasticity, memory, and cognitive learning. Sialoglycoprotein associated with cones and rods (SPACRCAN), an HA binding CSPG, stabilizes the inter‐photoreceptor ECM. HSPGs pikachurin and eyes shut stabilize the photoreceptor synapse aiding in phototransduction and neurotransduction with retinal bipolar neurons crucial to visual acuity. This is achieved through Laminin G motifs in pikachurin, eyes shut, and neurexins that interact with the dystroglycan–cytoskeleton–ECM‐stabilizing synaptic interconnections, neuronal interactive specificity, and co‐ordination of regulatory action potentials in neural networks.

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Cellular and pathological functions of tau

Parra Bravo,

Naguib,

Gan

2024

Nat Rev Mol Cell Biol

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Intracellular accumulation of tau oligomers in astrocytes and their synaptotoxic action rely on Amyloid Precursor Protein Intracellular Domain-dependent expression of Glypican-4

Cited by 4 publications

References 41 publications

Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach

Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach

CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity

Cellular and pathological functions of tau

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