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Alpha-synuclein and tau: teammates in neurodegeneration?

Moussaud S, Jones DR, Moussaud-Lamodière EL, Delenclos M, Ross OA, McLean PJ - Mol Neurodegener (2014)

Bottom Line: Moreover, tau and α-synuclein appear to promote the fibrillization and solubility of each other in vitro and in vivo.This suggests that interactions between tau and α-synuclein form a deleterious feed-forward loop essential for the development and spreading of neurodegeneration.Here, we review the recent literature with respect to elucidating the possible links between α-synuclein and tau.

View Article: PubMed Central - PubMed

Affiliation: Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA. McLean.Pamela@mayo.edu.

ABSTRACT
The accumulation of α-synuclein aggregates is the hallmark of Parkinson's disease, and more generally of synucleinopathies. The accumulation of tau aggregates however is classically found in the brains of patients with dementia, and this type of neuropathological feature specifically defines the tauopathies. Nevertheless, in numerous cases α-synuclein positive inclusions are also described in tauopathies and vice versa, suggesting a co-existence or crosstalk of these proteinopathies. Interestingly, α-synuclein and tau share striking common characteristics suggesting that they may work in concord. Tau and α-synuclein are both partially unfolded proteins that can form toxic oligomers and abnormal intracellular aggregates under pathological conditions. Furthermore, mutations in either are responsible for severe dominant familial neurodegeneration. Moreover, tau and α-synuclein appear to promote the fibrillization and solubility of each other in vitro and in vivo. This suggests that interactions between tau and α-synuclein form a deleterious feed-forward loop essential for the development and spreading of neurodegeneration. Here, we review the recent literature with respect to elucidating the possible links between α-synuclein and tau.

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Related in: MedlinePlus

Tau and α-synuclein pathologies. A to D- Histological sections from the amygdala of DLB patients immunostained with an antibody against phosphorylated tau (PHF-1, Abcam, #ab66275) (A and B) or an antibody against phosphorylated αsyn (pSyn#64, Wako, #015-25191) (C and D). Abnormal proteinaceous inclusions of phosphorylated tau protein, called neurofibrillary tangles (A and B,), and of αsyn protein, called Lewy bodies and neurites (C and D,) are often found in neurons of the amygdala in DLB patients.
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Fig3: Tau and α-synuclein pathologies. A to D- Histological sections from the amygdala of DLB patients immunostained with an antibody against phosphorylated tau (PHF-1, Abcam, #ab66275) (A and B) or an antibody against phosphorylated αsyn (pSyn#64, Wako, #015-25191) (C and D). Abnormal proteinaceous inclusions of phosphorylated tau protein, called neurofibrillary tangles (A and B,), and of αsyn protein, called Lewy bodies and neurites (C and D,) are often found in neurons of the amygdala in DLB patients.

Mentions: Interestingly, at the molecular level, protein misfolding, accumulation, aggregation and subsequently the formation of amyloid deposits are common features in many neurological disorders including AD and PD. Thus neurodegenerative diseases are sometimes referred to as proteinopathies [4]. The existence of a common mechanism suggests that neurodegenerative disorders likely share a common trigger and that the nature of the pathology is determined by the type of the aggregated protein and the localization of the cell affected (Figures 1, 2 and 3).Figure 1


Alpha-synuclein and tau: teammates in neurodegeneration?

Moussaud S, Jones DR, Moussaud-Lamodière EL, Delenclos M, Ross OA, McLean PJ - Mol Neurodegener (2014)

Tau and α-synuclein pathologies. A to D- Histological sections from the amygdala of DLB patients immunostained with an antibody against phosphorylated tau (PHF-1, Abcam, #ab66275) (A and B) or an antibody against phosphorylated αsyn (pSyn#64, Wako, #015-25191) (C and D). Abnormal proteinaceous inclusions of phosphorylated tau protein, called neurofibrillary tangles (A and B,), and of αsyn protein, called Lewy bodies and neurites (C and D,) are often found in neurons of the amygdala in DLB patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230508&req=5

Fig3: Tau and α-synuclein pathologies. A to D- Histological sections from the amygdala of DLB patients immunostained with an antibody against phosphorylated tau (PHF-1, Abcam, #ab66275) (A and B) or an antibody against phosphorylated αsyn (pSyn#64, Wako, #015-25191) (C and D). Abnormal proteinaceous inclusions of phosphorylated tau protein, called neurofibrillary tangles (A and B,), and of αsyn protein, called Lewy bodies and neurites (C and D,) are often found in neurons of the amygdala in DLB patients.
Mentions: Interestingly, at the molecular level, protein misfolding, accumulation, aggregation and subsequently the formation of amyloid deposits are common features in many neurological disorders including AD and PD. Thus neurodegenerative diseases are sometimes referred to as proteinopathies [4]. The existence of a common mechanism suggests that neurodegenerative disorders likely share a common trigger and that the nature of the pathology is determined by the type of the aggregated protein and the localization of the cell affected (Figures 1, 2 and 3).Figure 1

Bottom Line: Moreover, tau and α-synuclein appear to promote the fibrillization and solubility of each other in vitro and in vivo.This suggests that interactions between tau and α-synuclein form a deleterious feed-forward loop essential for the development and spreading of neurodegeneration.Here, we review the recent literature with respect to elucidating the possible links between α-synuclein and tau.

View Article: PubMed Central - PubMed

Affiliation: Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA. McLean.Pamela@mayo.edu.

ABSTRACT
The accumulation of α-synuclein aggregates is the hallmark of Parkinson's disease, and more generally of synucleinopathies. The accumulation of tau aggregates however is classically found in the brains of patients with dementia, and this type of neuropathological feature specifically defines the tauopathies. Nevertheless, in numerous cases α-synuclein positive inclusions are also described in tauopathies and vice versa, suggesting a co-existence or crosstalk of these proteinopathies. Interestingly, α-synuclein and tau share striking common characteristics suggesting that they may work in concord. Tau and α-synuclein are both partially unfolded proteins that can form toxic oligomers and abnormal intracellular aggregates under pathological conditions. Furthermore, mutations in either are responsible for severe dominant familial neurodegeneration. Moreover, tau and α-synuclein appear to promote the fibrillization and solubility of each other in vitro and in vivo. This suggests that interactions between tau and α-synuclein form a deleterious feed-forward loop essential for the development and spreading of neurodegeneration. Here, we review the recent literature with respect to elucidating the possible links between α-synuclein and tau.

Show MeSH
Related in: MedlinePlus