Parkinson's disease as a member of Prion-like disorders

Herva, María Eugenia; Spillantini, Maria Grazia

doi:10.1016/j.virusres.2014.10.016

Cited by 31 publications

(27 citation statements)

References 155 publications

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“…1 The main pathological features of PD are apoptosis of dopamine neurons and the formation of intracellular Lewy bodies in substantia nigra, 2 which further cause bradykinesia, muscular rigidity, resting tremor and mental abnormality. 1 The main pathological features of PD are apoptosis of dopamine neurons and the formation of intracellular Lewy bodies in substantia nigra, 2 which further cause bradykinesia, muscular rigidity, resting tremor and mental abnormality.…”

Section: Introductionmentioning

confidence: 99%

Inhibition effects of tanshinone on the aggregation of α-synuclein

Zhao

et al. 2016

Food Funct.

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Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Lewy bodies that are formed by the aggregated α-synuclein are a major pathological feature of PD. Salvia miltiorrhiza has been used as food and as a traditional medicine for centuries in China, with tanshinone I (TAN I) and tanshinone IIA (TAN IIA) as its major bioactive ingredients. Here, we investigated the effects of TAN I and TAN IIA on α-synuclein aggregation both in vitro and in a transgenic Caenorhabditis elegans PD model (NL5901). We demonstrated that TAN I and TAN IIA inhibited the aggregation of α-synuclein as demonstrated by the prolonged lag time and the reduced thioflavin-T fluorescence intensity; TAN I and TAN IIA also disaggregated preformed mature fibrils in vitro. Moreover, the presence of TAN I or TAN IIA affected the secondary structural transformation of α-synuclein from unstructured coils to β-sheets, and alleviated the membrane disruption caused by aggregated α-synuclein in vitro. Besides, the immuno-dot-blot assay indicated that TAN I and TAN IIA reduce the formation of oligomers and fibrils. We further found that TAN I and TAN IIA extended the life span of NL5901, a strain of transgenic C. elegans that expresses human α-synuclein, possibly by attenuating the aggregation of α-synuclein. Taken together, our results suggested that TAN I and TAN IIA may be explored further as potential candidates for the prevention and treatment of PD.

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Section: Introductionmentioning

confidence: 99%

Inhibition effects of tanshinone on the aggregation of α-synuclein

Zhao

et al. 2016

Food Funct.

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“…It is conceivable that, under these circumstances and possibly only for a short time, soluble aggregates of misfolded and hyperphosphorylated but nonfibrillar tau protein penetrate as far as the terminal branches of the axon and into presynaptic terminals, where they then become available for transport to the postsynaptic side of the synaptic cleft (Braak and Del Tredici 2015b). Were that to prove true, the pathological process would be transmissible to the successive neurons only via terminal axons and synaptic connections of involved nerve cells.These considerations and experimental data make it possible to associate the AD-and PD- (Prusiner 1982(Prusiner , 2012(Prusiner , 2013McBride et al 2001;Vella et al 2007;Aguzzi and Calella 2009;Aguzzi and Rajendran 2009;Guest et al 2011;Liberski 2012;Herva and Spillantini 2015). However, we prefer to use the term "prion-like" to differentiate sporadic AD and PD from rapidly progressive and infectious prion diseases, as PD and AD have not been shown to be rapidly progressive and contagious (Olanow and McNaught 2011;Iba 2013;Irwin et al 2013;Kaufman and Diamond 2013;Beekes et al 2014;Goedert et al 2014Goedert et al , 2015Brandel et al 2015;Walker and Jucker 2015;Walsh and Selkoe 2016).…”

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confidence: 99%

Potential Pathways of Abnormal Tau and α-Synuclein Dissemination in Sporadic Alzheimer's and Parkinson's Diseases

Braak

Tredici

2016

Cold Spring Harb Perspect Biol

105

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Experimental data indicate that transneuronal propagation of abnormal protein aggregates in neurodegenerative proteinopathies, such as sporadic Alzheimer's disease (AD) and Parkinson's disease (PD), is capable of a self-propagating process that leads to a progression of neurodegeneration and accumulation of prion-like particles. The mechanisms by which misfolded tau and a-synuclein possibly spread from one involved nerve cell to the next in the neuronal chain to induce abnormal aggregation are still unknown. Based on findings from studies of human autopsy cases, we review potential pathways and mechanisms related to axonal and transneuronal dissemination of tau (sporadic AD) and a-synuclein (sporadic PD) aggregates between anatomically interconnected regions. S poradic Alzheimer's disease (AD) and Parkinson's disease (PD) are human neurodegenerative disorders that do not occur in other vertebrate species. Pathological hallmark lesions in AD and PD involve only a few types of nerve cells, mainly projection neurons. These lesions develop at predetermined predilection sites and progress according to predictable patterns (Braak and Del Tredici 2009, 2015). In AD, disease-related lesions remain confined to the central nervous system (CNS), whereas in PD they develop not only in the CNS but also in the enteric (ENS) and peripheral (PNS) nervous systems. Both diseases are caused by misfolding of specific proteins that are associated with aberrant aggregation. AD is primarily characterized by pathological forms of the intraneuronal protein tau (Goedert et al. 2006;Iqbal et al. 2009) and, thereafter gradually, by extracellular deposits of the b-amyloid protein (Ab) (Alafuzoff et al. 2009;Haass et al. 2012;Masters and Selkoe 2012). In mature nerve cells, the highest concentrations of the protein tau usually are found in the axon. Key lesions in sporadic PD consist of aggregated forms of a-synuclein, a protein located chiefly in axons and their presynaptic terminals (Eisenberg and Jucker 2012;Jucker and Walker 2013;Kaufman and Diamond 2013;Goedert et al. 2014). Notably, all brain regions and all types of nerve cells consecutively involved in AD or PD are anatomically interconnected over considerable distances, thereby indicating that physical contact among such interconnected nerve cells plays a key role in the pathogenesis of both illnesses (Pearson et al. 1985;Saper et al. 1987;Pearson and Powell 1989;Pearson 1996;Duyckaerts et al. 1997;Braak and Del Tredici 2011b). Ab is deposited extracellularly and thus is not known to transfer from one nerve cell to the next in the neuronal chain (Fiala 2007;Kaufman and Diamond 2013).Here, we focus on potential pathways and mechanisms related to the postulated transmission and transneuronal dissemination of tau and a-synuclein between involved neurons and as yet uninvolved neurons in anatomically connected regions (Brundin et al. 2008Clavaguera et al. 2009Clavaguera et al. , 2013aDesplats et al. 2009;Luk et al. 2009;Angot et al. 2010 Angot et al. , 2012Frost and Diamond 2010;Goedert...

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“…More recently, the ability of tau to propagate transsynaptically through well‐established brain anatomical pathways has been reported, including AD and FTLD cases with argyrophilic grain pathology . Experimental support for the existence of a cell‐to‐cell transfer of α ‐syn inclusions has come from the seminal research showing that misfolded intraneuronal α ‐syn can transfer to neighboring cells both in culture and in the brains of patients with PD who had received fetal mesencephalic nerve cell transplants 11–16 years earlier revealing the presence of LB in the grafts . Then, several in vitro and in vivo studies suggested that α ‐syn can undergo a toxic template conformational change, spread from cell to cell and from region to region, and initiate the formation of LB‐like aggregates, contributing to the PD pathogenesis .…”

Section: Clinical Phenotypes Molecules and Pathology Of Neurodegenementioning

confidence: 99%

“…Experimental support for the existence of a cell‐to‐cell transfer of α ‐syn inclusions has come from the seminal research showing that misfolded intraneuronal α ‐syn can transfer to neighboring cells both in culture and in the brains of patients with PD who had received fetal mesencephalic nerve cell transplants 11–16 years earlier revealing the presence of LB in the grafts . Then, several in vitro and in vivo studies suggested that α ‐syn can undergo a toxic template conformational change, spread from cell to cell and from region to region, and initiate the formation of LB‐like aggregates, contributing to the PD pathogenesis . Whereas a cell‐to‐cell transmission of TDP‐43 has not been demonstrated conclusively, a recently discovered C‐terminal prion‐like domain has been implicated in the aggregation of TDP‐43 in cultured cells from diseased brains .…”

Section: Clinical Phenotypes Molecules and Pathology Of Neurodegenementioning

confidence: 99%

Propagation of Pathology through Brain Networks in Neurodegenerative Diseases: From Molecules to Clinical Phenotypes

Weiler

Filippi

2015

CNS Neurosci Ther

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The cellular mechanisms underlying the stereotypical progression of pathology in neurodegenerative diseases are incompletely understood, but increasing evidence indicates that misfolded protein aggregates can spread by a self-perpetuating neuron-to-neuron transmission. Novel neuroimaging techniques can help elucidating how these disorders spread across brain networks. Recent knowledge from structural and functional connectivity studies suggests that the relation between neurodegenerative diseases and distinct brain networks is likely to be a strict consequence of diffuse network dynamics. Diffusion tensor magnetic resonance imaging also showed that measurement of white matter tract involvement can be a valid surrogate to assess the in vivo spreading of pathological proteins in these conditions. This review will introduce briefly the main molecular and pathological substrates of the most frequent neurodegenerative diseases and provide a comprehensive overview of neuroimaging findings that support the "network-based neurodegeneration" hypothesis in these disorders. Characterizing network breakdown in neurodegenerative diseases will help anticipate and perhaps prevent the devastating impact of these conditions.

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Parkinson's disease as a member of Prion-like disorders

Cited by 31 publications

References 155 publications

Inhibition effects of tanshinone on the aggregation of α-synuclein

Inhibition effects of tanshinone on the aggregation of α-synuclein

Potential Pathways of Abnormal Tau and α-Synuclein Dissemination in Sporadic Alzheimer's and Parkinson's Diseases

Propagation of Pathology through Brain Networks in Neurodegenerative Diseases: From Molecules to Clinical Phenotypes

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