Protein Aggregation and Neurodegeneration: Tauopathies and Synucleinopathies

Goedert, Michel

doi:10.1002/9781118661895.ch2

Cited by 3 publications

(4 citation statements)

References 253 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other researchers have also reported similar results, 21 suggesting a possible role of prion-like spreading of pathology in the brain in various neurodegenerative diseases. 4 Furthermore, we also showed that not only alphasynuclein, but also tau is deposited in mice injected with synthetic alpha-synuclein fibrils into striatum. 12 In these mouse brains, phosphorylated tau aggregates were rarely co-localized with alpha-synuclein pathology, which is very similar to the above results obtained using cultured cells expressing tau and treated with alpha-synuclein fibrils.…”

Section: Depositionmentioning

confidence: 62%

“…[1][2][3] Prion-like propagation of intracellular protein aggregates has been suggested to account for the spreading of these pathologies and progression of the diseases. [4][5][6][7] In pure cases, a single typical pathology can be seen in the diseased brain, in which aggregates composed of one abnormal protein characteristic of the disease are accumulated. However, in many cases, patients exhibit aggregation of multiple pathological proteins.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular mechanisms of the co‐deposition of multiple pathological proteins in neurodegenerative diseases

2017

View full text Add to dashboard Cite

Intracellular inclusions composed of abnormal protein aggregates are one of the neuropathological features of neurodegenerative diseases, and the formation of intracellular aggregates is believed to be associated with neurodegeneration leading to the onset of these diseases. In typical or pure cases, characteristic pathologies with one particular protein, such as tau, alpha-synuclein or transactivation response DNA protein 43 (TDP-43), can be observed in brains of patients. On the other hand, multiple protein pathologies co-exist in many cases, raising the possibility that they may influence each other reciprocally in the pathogenesis and progression of the diseases. However, the molecular mechanisms through which these proteins interact with each other and through which they are co-deposited in brains of patients remain poorly understood. In this review, we focus on the mechanisms of deposition of multiple pathological proteins, such as tau, alphasynuclein and/or TDP-43, and on co-deposition models of these proteins in vitro and in vivo intended to recapitulate the multiple pathologies found in diseased brains.

show abstract

Section: Depositionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of the co‐deposition of multiple pathological proteins in neurodegenerative diseases

2017

View full text Add to dashboard Cite

show abstract

“…These findings support the Braak hypothesis based upon autopsy studies, that predicted GI symptoms in the pre-motor phase, and that PD spreads in a rostrocaudal manner from the enteric nervous system (ENS) to the central nervous system (CNS) via vagal pathways [16,17]. Since its publication, Braak's hypothesis has received critiques (summarized in [18]), and some more recent data to argue that the disease originates in the brain [19] along with a large body of supportive evidence [20][21][22][23][24][25][26]. A recent review of autopsy studies from a large series has confirmed the predictions of the Braak hypothesis [27] and also the notion that there could be 2 different subtypes of PD, one that is body-first subtype and another that is brain-first subtype [28].…”

Section: Pathophysiologymentioning

confidence: 99%

An Update on Medical and Surgical Treatments of Parkinson’s Disease

2021

View full text Add to dashboard Cite

Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta and other neuronal populations. The worldwide prevalence of PD is over 7 million and has been increasing more rapidly than many other neurodegenerative disorders. PD symptoms can be broadly divided into motor (slowness, stiffness, tremor) and non-motor symptoms (such as depression, dementia, psychosis, orthostatic hypotension). Patients can also have prodromal symptoms of rapid eye movement sleep behavior disorder, hyposmia, and constipation. The diagnosis of PD is mainly clinical, but dopamine transporter singlephoton emission computed tomography can improve the accuracy of the diagnosis. Dopamine based therapies are used for the treatment of motor symptoms. Non-motor symptoms are treated with other medications such as selective serotonin reuptake inhibitors (depression/anxiety), acetylcholinesterase inhibitors (dementia), and atypical antipsychotics (psychosis). Patients with motor fluctuations or uncontrolled tremor, benefit from deep brain stimulation. Levodopa-carbidopa intestinal gel is an alternative to deep brain stimulation for uncontrolled motor fluctuations. Rehabilitative therapies such as physical, occupational, and speech therapy are important during all stages of the disease. Management of PD is complex but there have been significant advancements in the treatment of motor and non-motor symptoms over the past few years. This review discusses the updates in the medical and surgical management of PD.

show abstract

“…It may occur due to various causes, including the accumulation of protein aggregates such as amyloid beta (Aβ) or tau, oxidative stress, and genetic mutations ( Hoeijmakers, 2009 ; Chang et al, 2018 ). Pathologies of neurodegenerative diseases like Alzheimer’s are generally characterized by the accumulation of insoluble extracellular aggregates such as Aβ aggregates in specific brain regions ( Goedert, 2007 ). Aβ is a protein fragment caused by the wrong process of a protein called amyloid precursor protein (APP).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the different isoforms of vitamin e against amyloid beta-induced neurodegeneration

ÖZDEMİR¹,

ÇETİN²,

ONUR³

2022

Turkish Journal of Biology

View full text Add to dashboard Cite

Neurodegeneration is the progressive loss of structure or function of neurons. Amyloid beta oligomers and aggregates have been linked to neurodegeneration. While previous studies have suggested that dietary α-tocopherol intake can prevent amyloid beta aggregation and protect the brain against neurotoxicity, other research, however, indicated that tocotrienol forms might be used as an alternate agent against this kind of degeneration. In the presented research, we compared the in vitro protective effects of α-tocopherol and α-tocotrienol. In this context, we formed an in vitro neurodegeneration model with primary isolated neurons and measured α-tocopherol’s and α-tocotrienol’s protective effects. As a result, α-tocopherol and α-tocotrienol prevent the degeneration of neurons. Moreover, α-tocopherol and α-tocotrienol regulated the neuron’s calcium channels mechanism by decreasing the expression of the calcium channel alpha 1C subunit. We also observed that the amount of amyloid beta accumulation in the extracellular matrix decreased with the application of these isoforms. In specific time points, α-tocopherol and α-tocotrienol differ in terms of protective effects. In conclusion, it could be interpreted that, in more extended periods, α-tocotrienol could be a significant protective agent against amyloid beta-induced neurodegeneration, and it can be used as an alternative to other protective agents, especially α-tocopherol.

show abstract

Protein Aggregation and Neurodegeneration: Tauopathies and Synucleinopathies

Cited by 3 publications

References 253 publications

Molecular mechanisms of the co‐deposition of multiple pathological proteins in neurodegenerative diseases

Molecular mechanisms of the co‐deposition of multiple pathological proteins in neurodegenerative diseases

An Update on Medical and Surgical Treatments of Parkinson’s Disease

Comparison of the different isoforms of vitamin e against amyloid beta-induced neurodegeneration

Contact Info

Product

Resources

About