PAMAM Dendrimers as Potential Agents against Fibrillation of<i>α</i>‐Synuclein, a Parkinson's Disease‐Related Protein

Rekas, Agata; Lo, Victor; Gadd, Geoffrey Michael; Cappai, Roberto; Yun, Seok Il

doi:10.1002/mabi.200800242

Cited by 65 publications

(37 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another class of compounds exerting anti-aggregation effects includes polyamidoamine (PAMAM) dendrimers—highly branched polymers possessing a well-defined spherical geometry 109 . PAMAM dendrimers (generations G3, G4, and G5) inhibit fibrillization of α-synuclein and promote the breakdown of pre-existing fibrils.…”

Section: In Vitro Aggregation Assays Of α-Synucleinmentioning

confidence: 99%

In vitro aggregation assays for the characterization of α-synuclein prion-like properties

Narkiewicz

Giachin

Legname

2014

Prion

View full text Add to dashboard Cite

Aggregation of α-synuclein plays a crucial role in the pathogenesis of synucleinopathies, a group of neurodegenerative diseases including Parkinson disease (PD), dementia with Lewy bodies (DLB), diffuse Lewy body disease (DLBD) and multiple system atrophy (MSA). The common feature of these diseases is a pathological deposition of protein aggregates, known as Lewy bodies (LBs) in the central nervous system. The major component of these aggregates is α-synuclein, a natively unfolded protein, which may undergo dramatic structural changes resulting in the formation of β-sheet rich assemblies. In vitro studies have shown that recombinant α-synuclein protein may polymerize into amyloidogenic fibrils resembling those found in LBs. These aggregates may be uptaken and propagated between cells in a prion-like manner. Here we present the mechanisms and kinetics of α-synuclein aggregation in vitro, as well as crucial factors affecting this process. We also describe how PD-linked α-synuclein mutations and some exogenous factors modulate in vitro aggregation. Furthermore, we present a current knowledge on the mechanisms by which extracellular aggregates may be internalized and propagated between cells, as well as the mechanisms of their toxicity.

show abstract

Section: In Vitro Aggregation Assays Of α-Synucleinmentioning

confidence: 99%

In vitro aggregation assays for the characterization of α-synuclein prion-like properties

Narkiewicz

Giachin

Legname

2014

Prion

View full text Add to dashboard Cite

show abstract

“…Rekas et al (2009) [124] observed the effect of PAMAM dendrimers (generations 3.0, 4.0 and 5.0) on the fibrillation of alpha-synuclein and found that PAMAM dendrimers suppressed the fibrillation and this effect was increased with both PAMAM concentration and generation number. They also found that as the PAMAM concentration increased there were structural changes in the formed aggregates of alpha-synuclein from cylindrical to dense three-dimensional ones.…”

Section: Treatment Strategies For Brain Diseases Using Dendrimersmentioning

confidence: 97%

Targeted Brain Delivery of Bioactive Molecules Using Nanocarriers

Kr¹,

Gajbhiye²,

Soni³

2015

J Bioequiv Availab

View full text Add to dashboard Cite

Delivery of the bioactives to the brain is the utmost challenging task to cope with brain diseases. Brain is protected with blood brain barrier, blood-CSF barrier and efflux systems, which controls the entry of body as well as foreign compounds to access the brain cells. Only nutrients, which are essential for normal metabolism, can enter into the brain. In the shadow of this fact new strategies are being investigated to facilitate the entry of administered therapeutic compound into the brain. Active targeting is a evolving approach, which uses ligand and suitable carrier for the site-specific delivery and is being recently achieved by the use of nanocarriers. These nanocarriers are nanosized systems, which act as a cargo for the encapsulated drugs. At the same time, endo-or exogenous ligand can be attached to these nanocarriers to recognize specific receptors on brain capillary endothelium leading to delivery of drug in the vicinity of brain cells. Their potential is under immense investigation to increase the therapeutics outcome in the treatment of brain related problems. This review deals with the recent advances in nanocarriers based novel strategies for effective brain specific delivery.

show abstract

“…PAMAM dendrimers (generations (G) 4, 5 and 6) used as purchased without modification were able to reduce ␣-synuclein fibrillation as measured by the Thioflavin T assay [238]. This occurred for all three generations, and the effect of concentration analyzed for G5 PAMAM showed a concentration dependence on the degree of inhibition.…”

Section: Polymeric Inhibitors Of Protein Aggregationmentioning

confidence: 99%

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

Newland

Werner

et al. 2015

Progress in Polymer Science

View full text Add to dashboard Cite

a b s t r a c tParkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and represents a growing health burden to western societies. Like many neurodegenerative disorders the cause is unknown, however, as the pathogenesis becomes ever more elucidated, it is becoming clear that effective delivery is a key issue for new therapeutics. The versatility of today's polymerization techniques allows the synthesis of a wide range of polymer materials which hold great potential to aid in the delivery of small molecules, proteins, genetic material or cells. In this review, we capture the recent advances in polymer based therapeutics of the central nervous system (CNS). We place the advances in historical context and, furthermore, provide future prospects in line with newly discovered advancements in the understanding of PD and other neurodegenerative disorders. This review provides researchers in the field of polymer chemistry and materials science an up-to-date understanding of the requirements placed upon materials designed for use in the CNS aiding the focus of polymer therapeutic design.

show abstract

PAMAM Dendrimers as Potential Agents against Fibrillation ofα‐Synuclein, a Parkinson's Disease‐Related Protein

Cited by 65 publications

References 29 publications

In vitro aggregation assays for the characterization of α-synuclein prion-like properties

In vitro aggregation assays for the characterization of α-synuclein prion-like properties

Targeted Brain Delivery of Bioactive Molecules Using Nanocarriers

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

Contact Info

Product

Resources

About