Systemic amyloidosis

Wechalekar, Ashutosh; Gillmore, Julian D.; Hawkins, Philip N.

doi:10.1016/s0140-6736(15)01274-x

Cited by 761 publications

(716 citation statements)

References 142 publications

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“…16,17 For the first time, however, we have observed a reduction in 6-month mortality from 37% to 24%. Our data would suggest that these improvements relate to a growing availability of effective treatments and potentially better baseline disease characteristics resulting from earlier diagnosis.…”

Section: Discussionmentioning

confidence: 60%

“…14,15 The survival of patients with AL amyloidosis has improved over time, but 6-month mortality had largely remained unchanged over multiple decades. 16,17 In light of major advances in recent years, we aimed to study the trends in patients and disease characteristics, treatment use, and outcome in 1551 newly diagnosed AL amyloidosis patients seen in our institution between 2000 and 2014.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death

Muchtar¹,

Gertz²,

Kumar³

et al. 2017

Blood

265

203

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death

Muchtar¹,

Gertz²,

Kumar³

et al. 2017

Blood

265

203

View full text Add to dashboard Cite

show abstract

“…Many of the protein misfolding diseases ('proteopathies' or 'proteino pathies'), with the exception of systemic amyloid osis 108,109 , manifest primarily in the brain, causing neurological symptoms. The reason for this phenom enon is still elusive, but the onset of symptoms only at an advanced age and the notion that neurons are largely postmitotic, nonregenerating cells prompt specu lation about additional 'permissive' factors needed to precipitate disease, particularly given that distinct proteins are involved in various conditions.…”

Section: Derailment Owing To Genetic Mutationsmentioning

confidence: 99%

Proteostasis in cardiac health and disease

Henning

Brundel²

2017

Nat Rev Cardiol

132

113

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The worldwide increase in life expectancy gives rise to an increasing prevalence of cardiac diseases, which remain the leading cause of disability and death in the developed world [1][2][3] . Currently, the mechanisms under lying how ageing contributes to the initiation or acceler ation of cardiac diseases are essentially unresolved. Prevailing theories of ageing centre on gradual derail ment of cellular protein homeostasis -proteostasis -either by design (genetically) or by 'wear and tear' (environmentally) 3 . Central to the role of proteostasis derailment as a major factor in ageing is the observation that protein function declines over time.Proteins are the most versatile and complex macro molecules and are involved in the proper functioning of every biological process 4 . After synthesis as a poly peptide chain from the genetic code, proper function of a protein relies heavily on its correct folding into a 3D native state and on various post translational modifi cations, mostly involving the addition of chem ical groups (including phosphate, acetate, and carbo hydrate). Protein maturation, transport, and ultimately breakdown is monitored and supported by various classes of proteins, collectively called 'protein quality control' (PQC) [3][4][5] . Balanced proteostasis, therefore, depends on proper PQC and is crucial for cellular and organismal health 6 . The intricate network making up the PQC involves numerous proteins, of which the main players are the chaperones and their regula tors 4,7-9 (assisting in folding and refolding of proteins) and the pathways that clear irreversibly misfolded and aggregation prone proteins (the ubiquitin-proteasome system [UPS] and autophagy systems) 9-11 . With ageing, the gradual accumulation of misfolded or damaged pro teins, together with concomitant failure of PQC, results in proteotoxic stress and compromised defence against reactive oxygen species (ROS) 10 , a process that is likely to be accelerated in various age related diseases includ ing neurodegenerative diseases 12,13 , type 2 diabetes mel litus 14 , cancer 15 , and cardiac diseases [16][17][18][19][20] . In addition to the accumulation of misfolded proteins, ageing is accompanied by an imbalance in the proteome, as indi cated by lowered expression of chaperone, proteaso mal, ribosomal, and mitochondrial proteins, whereas proteins related to oxidative stress are upregulated 21,22 . Although mild impairment of proteostasis extends lifespan in Caenorhabditis elegans, referred to as hormesis, sustained impairment is accompanied by loss of PQC to neutralize this effect 3,5 . Importantly, evidence indicates that the amount of soluble, aggregate prone protein oligomers, rather than the abundance of pro tein aggregates, correlates with disease severity 23,24 . Therefore, protein aggregates, which contain both misfolded proteins and elevated levels of chaper ones, constitute an adequate PQC response, aimed at sequestering potentially harmful protein oligomers, rather than embodying the ultimate cellular threat 25 . This ...

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“…The disease can be localized or systemic and is classified according to the identity of the amyloid fibril-forming protein [1]. Once the presence of amyloidosis is confirmed in a tissue biopsy specimen, it is critical to identify the amyloid type accurately, as management differs substantially depending on the nature and source of the amyloid-forming protein, ranging from supportive care through to aggressive chemotherapy or organ transplantation [2].…”

Section: Introductionmentioning

confidence: 99%