scholarly journals Structural and Toxic Properties of Protein Aggregates: Towards a Molecular Understanding of Alzheimer's Disease

10.5772/20922 ◽  
2011 ◽  
Author(s):  
Lei Wang ◽  
Silvia Campioni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Aggregates

scholarly journals Imaging Alzheimer's disease-related protein aggregates in human cells using a selenium label

2010 ◽  
Vol 241 ◽  
pp. 012020 ◽  
Author(s):  
E K McGuire ◽  
M Motskin ◽  
T P J Knowles ◽  
C M Dobson ◽  
D W McComb ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Aggregates ◽  
Human Cells ◽  
Related Protein

scholarly journals Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer’s disease-like pathology in human cerebral organoids

2020 ◽  
Author(s):  
Dina Ivanyuk ◽  
María José Pérez ◽  
Vasiliki Panagiotakopoulou ◽  
Gabriele Di Napoli ◽  
Dario Brunetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Cortical Neurons ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Protein Aggregates ◽  
Neuronal Cultures ◽  
Loss Of Function ◽  
Proteotoxic Stress

AbstractMutations in pitrilysin metallopeptidase 1 (PITRM1), a mitochondrial protease involved in mitochondrial precursor processing and degradation, result in a slow-progressive syndrome, characterized by cerebellar ataxia, psychotic episodes and obsessive behavior as well as cognitive decline. To investigate the pathogenetic mechanisms of mitochondrial presequence processing, we employed cortical neurons and cerebral organoids generated from PITRM1 knockout human induced pluripotent stem cells (iPSCs). PITRM1 deficiency strongly induced mitochondrial unfolded protein response (UPRmt) and enhanced mitochondrial clearance in iPSC-derived neurons. Furthermore, we observed increased levels of amyloid precursor protein and amyloid β in PITRM1 knockout neurons. However, neither cell death nor protein aggregates were observed in 2D iPSC-derived cortical neuronal cultures. On the contrary, cerebral organoids generated from PITRM1 knockout iPSCs spontaneously developed over time pathological features of Alzheimer’s disease (AD), including accumulation of protein aggregates, tau pathology, and neuronal cell death. Importantly, we provide evidence for a protective role of UPRmt and mitochondrial clearance against impaired mitochondrial presequence processing and proteotoxic stress. In summary, we propose a novel concept of PITRM1-linked neurological syndrome whereby defects of mitochondrial presequence processing induce an early activation of UPRmt that, in turn, modulates cytosolic quality control pathways. Thus our work supports a mechanistic link between mitochondrial function and common neurodegenerative proteinopathies.

Antibody 9D5 Recognizes Oligomeric Pyroglutamate Amyloid-β in a Fraction of Amyloid-β Deposits in Alzheimer's Disease without Cross-Reactivity with other Protein Aggregates

2012 ◽  
Vol 29 (2) ◽  
pp. 361-371 ◽  
Author(s):  
Vivek Venkataramani ◽  
Oliver Wirths ◽  
Herbert Budka ◽  
Wolfgang Härtig ◽  
Gabor G. Kovacs ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Protein Aggregates ◽  
Cross Reactivity

Transmission of pathogenic protein aggregates in Alzheimer’s disease

2017 ◽  
Vol 51 (3) ◽  
pp. 368-371 ◽  
Author(s):  
A. L. Schwarzman ◽  
S. V. Sarantseva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Aggregates

Rhizolutin, a Novel 7/10/6‐Tricyclic Dilactone, Dissociates Misfolded Protein Aggregates and Reduces Apoptosis/Inflammation Associated with Alzheimer's Disease

2020 ◽  
Vol 132 (51) ◽  
pp. 23194-23198
Author(s):  
Yun Kwon ◽  
Jisu Shin ◽  
Kwangho Nam ◽  
Joon Soo An ◽  
Seung‐Hoon Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Aggregates ◽  
Misfolded Protein

The role of dispersible amyloid β-protein aggregates for Alzheimer’s disease and its therapy

2012 ◽  
Vol 18 (2) ◽  
pp. 93
Author(s):  
Dietmar R. Thal ◽  
Julia Steinmetz ◽  
Marcus Fändrich ◽  
Julia Reichwald ◽  
Matthias Staufenbiel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Protein Aggregates ◽  
Amyloid Β Protein ◽  
Β Protein

scholarly journals Neuropathological and Biomarker Findings in Parkinson’s Disease and Alzheimer’s Disease: From Protein Aggregates to Synaptic Dysfunction

2020 ◽  
pp. 1-15
Author(s):  
Yaroslau Compta ◽  
Tamas Revesz
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Amyloid Β ◽  
Protein Aggregates ◽  
Amyloid Β Peptide ◽  
Therapeutic Implications ◽  
Positron Emission ◽  
Synaptic Markers

There is mounting evidence that Parkinson’s disease (PD) and Alzheimer’s disease (AD) share neuropathological hallmarks, while similar types of biomarkers are being applied to both. In this review we aimed to explore similarities and differences between PD and AD at both the neuropathology and the biomarker levels, specifically focusing on protein aggregates and synapse dysfunction. Thus, amyloid-β peptide (Aβ) and tau lesions of the Alzheimer-type are common in PD and α-synuclein Lewy-type aggregates are frequent findings in AD. Modern neuropathological techniques adding to routine immunohistochemistry might take further our knowledge of these diseases beyond protein aggregates and down to their presynaptic and postsynaptic terminals, with potential mechanistic and even future therapeutic implications. Translation of neuropathological discoveries to the clinic remains challenging. Cerebrospinal fluid (CSF) and positron emission tomography (PET) markers of Aβ and tau have been shown to be reliable for AD diagnosis. Conversely, CSF markers of α-synuclein have not been that consistent. In terms of PET markers, there is no PET probe available for α-synuclein yet, while the AD PET markers range from consistent evidence of their specificity (amyloid imaging) to greater uncertainty of their reliability due to off-target binding (tau imaging). CSF synaptic markers are attractive, still needing more evidence, which currently suggests those might be non-specific markers of disease progression. It can be summarized that there is neuropathological evidence that protein aggregates of AD and PD are present both at the soma and the synapse. Thus, a number of CSF and PET biomarkers beyond α-synuclein, tau and Aβ might capture these different faces of protein-related neurodegeneration. It remains to be seen what the longitudinal outcomes and the potential value as surrogate markers of these biomarkers are.

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