Critical Molecular and Cellular Contributors to Tau Pathology
Tauopathies represent a group of neurodegenerative diseases including Alzheimer’s disease (AD) that are characterized by the deposition of filamentous tau aggregates in the brain. The pathogenesis of tauopathies starts from the formation of toxic ‘tau seeds’ from hyperphosphorylated tau monomers. Th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/2/190 |
| _version_ | 1797396527340060672 |
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| author | Liqing Song Evan A. Wells Anne Skaja Robinson |
| author_facet | Liqing Song Evan A. Wells Anne Skaja Robinson |
| author_sort | Liqing Song |
| collection | DOAJ |
| description | Tauopathies represent a group of neurodegenerative diseases including Alzheimer’s disease (AD) that are characterized by the deposition of filamentous tau aggregates in the brain. The pathogenesis of tauopathies starts from the formation of toxic ‘tau seeds’ from hyperphosphorylated tau monomers. The presence of specific phosphorylation sites and heat shock protein 90 facilitates soluble tau protein aggregation. Transcellular propagation of pathogenic tau into synaptically connected neuronal cells or adjacent glial cells via receptor-mediated endocytosis facilitate disease spread through the brain. While neuroprotective effects of glial cells—including phagocytotic microglial and astroglial phenotypes—have been observed at the early stage of neurodegeneration, dysfunctional neuronal-glial cellular communication results in a series of further pathological consequences as the disease progresses, including abnormal axonal transport, synaptic degeneration, and neuronal loss, accompanied by a pro-inflammatory microenvironment. Additionally, the discovery of microtubule-associated protein tau (<i>MAPT</i>) gene mutations and the strongest genetic risk factor of tauopathies—an increase in the presence of the ε2 allele of apolipoprotein E (<i>ApoE</i>)—provide important clues to understanding tau pathology progression. In this review, we describe the crucial signaling pathways and diverse cellular contributors to the progression of tauopathies. A systematic understanding of disease pathogenesis provides novel insights into therapeutic targets within altered signaling pathways and is of great significance for discovering effective treatments for tauopathies. |
| first_indexed | 2024-03-09T00:52:41Z |
| format | Article |
| id | doaj.art-896957f224ad4023982ed31b99ffa464 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T00:52:41Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-896957f224ad4023982ed31b99ffa4642023-12-11T17:05:49ZengMDPI AGBiomedicines2227-90592021-02-019219010.3390/biomedicines9020190Critical Molecular and Cellular Contributors to Tau PathologyLiqing Song0Evan A. Wells1Anne Skaja Robinson2Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USADepartment of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USADepartment of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USATauopathies represent a group of neurodegenerative diseases including Alzheimer’s disease (AD) that are characterized by the deposition of filamentous tau aggregates in the brain. The pathogenesis of tauopathies starts from the formation of toxic ‘tau seeds’ from hyperphosphorylated tau monomers. The presence of specific phosphorylation sites and heat shock protein 90 facilitates soluble tau protein aggregation. Transcellular propagation of pathogenic tau into synaptically connected neuronal cells or adjacent glial cells via receptor-mediated endocytosis facilitate disease spread through the brain. While neuroprotective effects of glial cells—including phagocytotic microglial and astroglial phenotypes—have been observed at the early stage of neurodegeneration, dysfunctional neuronal-glial cellular communication results in a series of further pathological consequences as the disease progresses, including abnormal axonal transport, synaptic degeneration, and neuronal loss, accompanied by a pro-inflammatory microenvironment. Additionally, the discovery of microtubule-associated protein tau (<i>MAPT</i>) gene mutations and the strongest genetic risk factor of tauopathies—an increase in the presence of the ε2 allele of apolipoprotein E (<i>ApoE</i>)—provide important clues to understanding tau pathology progression. In this review, we describe the crucial signaling pathways and diverse cellular contributors to the progression of tauopathies. A systematic understanding of disease pathogenesis provides novel insights into therapeutic targets within altered signaling pathways and is of great significance for discovering effective treatments for tauopathies.https://www.mdpi.com/2227-9059/9/2/190tauopathiesAlzheimer’s diseaseprion-like propagationtau self-aggregationendocytosisneuron-glial communication |
| spellingShingle | Liqing Song Evan A. Wells Anne Skaja Robinson Critical Molecular and Cellular Contributors to Tau Pathology Biomedicines tauopathies Alzheimer’s disease prion-like propagation tau self-aggregation endocytosis neuron-glial communication |
| title | Critical Molecular and Cellular Contributors to Tau Pathology |
| title_full | Critical Molecular and Cellular Contributors to Tau Pathology |
| title_fullStr | Critical Molecular and Cellular Contributors to Tau Pathology |
| title_full_unstemmed | Critical Molecular and Cellular Contributors to Tau Pathology |
| title_short | Critical Molecular and Cellular Contributors to Tau Pathology |
| title_sort | critical molecular and cellular contributors to tau pathology |
| topic | tauopathies Alzheimer’s disease prion-like propagation tau self-aggregation endocytosis neuron-glial communication |
| url | https://www.mdpi.com/2227-9059/9/2/190 |
| work_keys_str_mv | AT liqingsong criticalmolecularandcellularcontributorstotaupathology AT evanawells criticalmolecularandcellularcontributorstotaupathology AT anneskajarobinson criticalmolecularandcellularcontributorstotaupathology |