Pathogenic protein aggregates such as β-amyloid and α-synuclein trigger microglial NLRP3 activation, leading to caspase-1 activation and IL-1β secretion.
Neurodegenerative disorders of the aging population are characterized by progressive accumulation of neuronal proteins such as α-synuclein (α-syn) in Parkinson's Disease (PD) and Amyloid ß (Aß) and Tau in Alzheimer's disease (AD) for which no treatments are currently available.
The details of trafficking and processing of APP to Aβ, the cytosolic intracellular Aβ domain (AICD) and small soluble proteins are shown, together with other amyloid-forming proteins such as tau and α-synuclein (α-syn).
This perspective article outlines mechanisms of mitochondrial import and protein degradation and how these have been linked to alpha-synuclein and Amyloid beta (Aβ) homeostasis.
Many neurodegenerative diseases are characterized by progressive loss of neurons and abnormal protein accumulation, including amyloid (A)β and tau in Alzheimer's disease and Lewy bodies and α-synuclein (α-syn) in Parkinson's disease (PD).
Therefore, nanoparticles binding can effectively restrain fibrillation of β-amyloid and α-synuclein proteins and eventually prevent the toxicity of pathogenesis peptide of Alzheimer.
In particular, brain aging presents characteristic patterns of misfolded oligomers, primarily constituted of β-amyloid (Aβ), tau, and α-synuclein (α-syn), which can accumulate in neuronal membranes or extracellular compartments.
While extensive biophysical and biochemical studies have been focused on IAPP and αS interacting with cell membranes or model lipid vesicles, the roles of plasma proteins on the amyloidosis and membrane association of these two major types of amyloid proteins have rarely been examined.
Using a combination of DNA PAINT and an amyloid-specific aptamer, we demonstrate that this technique is able to detect and super-resolve a range of aggregated species, including those formed by α-synuclein and amyloid-β.
We also emphasize the recent investigations on residual secondary structure formation in dynamic conformational ensembles of amyloid-β and α-synuclein, such as β-structure linked to the oligomerization and fibrillation mechanisms related to the pathologies of Alzheimer's and Parkinson's diseases.
Here, we describe the CSA in detail and outline its utility for distinguishing prion strains as well as unique conformational states of Aβ and α-synuclein aggregates.
Phosphorylated tau/α-synuclein and phosphorylated tau/amyloid-ß1-42+α-synuclein were higher in patients than in controls of the Parkinson's Progression Markers Initiative database.
These diseases are influenced by multiple genetic and environmental factors and share similar mechanisms as both are characterized by accumulation and aggregation of misfolded proteins - amyloid-beta (Aβ) in AD and α-synuclein in PD.
The aggregation of the intrinsically disordered protein alpha-synuclein (αS) into amyloid fibrils is thought to play a central role in the pathology of Parkinson's disease.
In pathological situations, TPPPs interact with α-synuclein and β-amyloid and promote their aggregation leading to Parkinson's disease and multiple system atrophy.