Universität zu Köln

Bell, Michael and Zempel, Hans (2022). SH-SY5Y-derived neurons: a human neuronal model system for investigating TAU sorting and neuronal subtype-specific TAU vulnerability. Rev. Neurosci., 33 (1). S. 1 - 16. BERLIN: WALTER DE GRUYTER GMBH. ISSN 2191-0200

Full text not available from this repository.

Abstract

The microtubule-associated protein (MAP) TAU is mainly sorted into the axon of healthy brain neurons. Somatodendritic missorting of TAU is a pathological hallmark of many neurodegenerative diseases, including Alzheimer's disease (AD). Cause, consequence and (patho)physiological mechanisms of TAU sorting and missorting are understudied, in part also because of the lack of readily available human neuronal model systems. The human neuroblastoma cell line SH-SY5Y is widely used for studying TAU physiology and TAU-related pathology in AD and related tauopathies. SH-SY5Y cells can be differentiated into neuron-like cells (SH-SY5Y-derived neurons) using various substances. This review evaluates whether SH-SY5Y-derived neurons are a suitable model for (i) investigating intracellular TAU sorting in general, and (ii) with respect to neuron subtype-specific TAU vulnerability. (I) SH-SY5Y-derived neurons show pronounced axodendritic polarity, high levels of axonally localized TAU protein, expression of all six human brain isoforms and TAU phosphorylation similar to the human brain. As SH-SY5Y cells are highly proliferative and readily accessible for genetic engineering, stable transgene integration and leading-edge genome editing are feasible. (II) SH-SY5Y-derived neurons display features of subcortical neurons early affected in many tauopathies. This allows analyzing brain region-specific differences in TAU physiology, also in the context of differential vulnerability to TAU pathology. However, several limitations should be considered when using SH-SY5Y-derived neurons, e.g., the lack of clearly defined neuronal subtypes, or the difficulty of mimicking age-related tauopathy risk factors in vitro. In brief, this review discusses the suitability of SH-SY5Y-derived neurons for investigating TAU (mis)sorting mechanisms and neuron-specific TAU vulnerability in disease paradigms.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bell, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Zempel, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-563161
DOI:	10.1515/revneuro-2020-0152
Journal or Publication Title:	Rev. Neurosci.
Volume:	33
Number:	1
Page Range:	S. 1 - 16
Date:	2022
Publisher:	WALTER DE GRUYTER GMBH
Place of Publication:	BERLIN
ISSN:	2191-0200
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MICROTUBULE-ASSOCIATED PROTEIN; AXON INITIAL SEGMENT; NEUROBLASTOMA-CELL-LINE; PAIRED-HELICAL-FILAMENT; ACID-INDUCED DIFFERENTIATION; MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; IN-VITRO MODEL; ALZHEIMERS-DISEASE; RETINOIC ACID Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56316