2017
DOI: 10.1101/cshperspect.a024133
|View full text |Cite
|
Sign up to set email alerts
|

Biological Spectrum of Amyotrophic Lateral Sclerosis Prions

Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD) are two neurodegenerative diseases with distinct clinical features but common genetic causes and neuropathological signatures. Ten years after the RNA-binding protein TDP-43 was discovered as the main protein in the cytoplasmic inclusions that characterize ALS and FTLD, their pathogenic mechanisms have never seemed more complex. Indeed, discoveries of the past decade have revolutionized our understanding of these diseases, highlightin… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

1
16
0

Year Published

2017
2017
2022
2022

Publication Types

Select...
8
1

Relationship

1
8

Authors

Journals

citations
Cited by 25 publications
(17 citation statements)
references
References 210 publications
(277 reference statements)
1
16
0
Order By: Relevance
“…ALS is the most common form of motor neuron disease (MND), affecting upper and lower motor neurons and ultimately leading to progressive paralysis. FTD is the second most common form of dementia after Alzheimer's disease 2 and is characterized by severe atrophy of frontal and temporal lobes and is, therefore, also referred to as frontotemporal lobar degeneration (FTLD).…”
Section: Introductionmentioning
confidence: 99%
“…ALS is the most common form of motor neuron disease (MND), affecting upper and lower motor neurons and ultimately leading to progressive paralysis. FTD is the second most common form of dementia after Alzheimer's disease 2 and is characterized by severe atrophy of frontal and temporal lobes and is, therefore, also referred to as frontotemporal lobar degeneration (FTLD).…”
Section: Introductionmentioning
confidence: 99%
“…TDP-43 prionoid proteins express ordered, self-perpetuating aggregation transmissible from affected cells to their progeny. Their properties suggest a closer relation to yeast prions than human prion protein (PrP; Polymenidou and Cleveland, 2017).…”
Section: Prionoid Neurodegenerative Disorders Afflicting Humansmentioning
confidence: 99%
“…Increased levels of TDP-43 mRNA have been observed in the motor neurons of both fALS and sALS patients, with TDP-43 aggregates forming in their motor cortices and spinal cords (Arai et al, 2006; Rabin et al, 2010; Qin et al, 2014). The development of TDP-43 inclusions results in increased export of TDP-43 from the nucleus to the cytoplasm, leading to a sustained decrease of nuclear TDP-43 and increased levels of stable TDP-43 mRNAs (Polymenidou and Cleveland, 2017). Upon moving into the cytoplasm, TDP-43 undergoes defective phosphorylation and conformational changes followed by ubiquitination, preventing re-entry into the nuclear compartment (Neumann et al, 2006, 2009; Ayala et al, 2008; Braak et al, 2017).…”
Section: Prionoid Neurodegenerative Disorders Afflicting Humansmentioning
confidence: 99%
“…The assemblies then recruit native proteins, turning them into misfolded forms. This self-perpetuation of misfolding proteins is a “twisted version of classical prion replication” that leads to amplification of pathological protein complexes that spread throughout the neuraxis, offering a pathogenic principle that underlies the rapid disease progression that characterizes ALS, and other neurodegenerative diseases[ 72 ].…”
Section: Prion-like Proteinsmentioning
confidence: 99%