Abstract
Amyloidoses are heterogeneous diseases that result from the deposition of toxic insoluble β-sheet fibrillar protein aggregates in different tissues. The cascade of molecular events leading to amyloidoses and to the related clinical manifestations is not completely understood. Nevertheless, it is known that tissue damage associated to this disease involves alteration of tissue architecture, interaction with cell surface receptors, inflammation elicited by the amyloid protein deposition, oxidative stress, and apoptosis. However, another important aspect to consider is that systemic protein massive deposition not only subverts tissue architecture but also determines a progressive cellular hypertrophy and dilation of the extracellular space enlarging the volume of the organ. Such an alteration increases the distance between cells and vessels with a drop in pO2 that, in turn, causes both necrotic cell death and activation of the hypoxia transcription factor HIF-1α. Herewith, we propose the hypothesis that both cell death and hypoxia represent two important events for the pathogenesis of damage and progression of amyloidoses. In fact, molecules released by necrotic cells activate inflammatory cells from one side while binding to HIF-1α-dependent membrane receptors expressed on hypoxic parenchymal cells on the other side. This latter event generates a signaling cascade triggering NFκB activation and chronic inflammation. Finally, we also suggest that this scenario, once proved and detailed, might suggest important targets for new therapeutic interventions.
| Original language | English |
|---|---|
| Article number | 7935310 |
| Pages (from-to) | 1-11 |
| Number of pages | 11 |
| Journal | Oxidative Medicine and Cellular Longevity |
| Volume | 2019 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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ASJC Scopus subject areas
- Biochemistry
- Ageing
- Cell Biology
Cite this
Hypoxia and inflammation as a consequence of β-fibril accumulation : A perspective view for new potential therapeutic targets. / Russo, Matteo A.; Tomino, Carlo; Vernucci, Enza; Limana, Federica; Sansone, Luigi; Frustaci, Andrea; Tafani, Marco.
In: Oxidative Medicine and Cellular Longevity, Vol. 2019, 7935310, 01.01.2019, p. 1-11.Research output: Contribution to journal › Review article
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TY - JOUR
T1 - Hypoxia and inflammation as a consequence of β-fibril accumulation
T2 - A perspective view for new potential therapeutic targets
AU - Russo, Matteo A.
AU - Tomino, Carlo
AU - Vernucci, Enza
AU - Limana, Federica
AU - Sansone, Luigi
AU - Frustaci, Andrea
AU - Tafani, Marco
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Amyloidoses are heterogeneous diseases that result from the deposition of toxic insoluble β-sheet fibrillar protein aggregates in different tissues. The cascade of molecular events leading to amyloidoses and to the related clinical manifestations is not completely understood. Nevertheless, it is known that tissue damage associated to this disease involves alteration of tissue architecture, interaction with cell surface receptors, inflammation elicited by the amyloid protein deposition, oxidative stress, and apoptosis. However, another important aspect to consider is that systemic protein massive deposition not only subverts tissue architecture but also determines a progressive cellular hypertrophy and dilation of the extracellular space enlarging the volume of the organ. Such an alteration increases the distance between cells and vessels with a drop in pO2 that, in turn, causes both necrotic cell death and activation of the hypoxia transcription factor HIF-1α. Herewith, we propose the hypothesis that both cell death and hypoxia represent two important events for the pathogenesis of damage and progression of amyloidoses. In fact, molecules released by necrotic cells activate inflammatory cells from one side while binding to HIF-1α-dependent membrane receptors expressed on hypoxic parenchymal cells on the other side. This latter event generates a signaling cascade triggering NFκB activation and chronic inflammation. Finally, we also suggest that this scenario, once proved and detailed, might suggest important targets for new therapeutic interventions.
AB - Amyloidoses are heterogeneous diseases that result from the deposition of toxic insoluble β-sheet fibrillar protein aggregates in different tissues. The cascade of molecular events leading to amyloidoses and to the related clinical manifestations is not completely understood. Nevertheless, it is known that tissue damage associated to this disease involves alteration of tissue architecture, interaction with cell surface receptors, inflammation elicited by the amyloid protein deposition, oxidative stress, and apoptosis. However, another important aspect to consider is that systemic protein massive deposition not only subverts tissue architecture but also determines a progressive cellular hypertrophy and dilation of the extracellular space enlarging the volume of the organ. Such an alteration increases the distance between cells and vessels with a drop in pO2 that, in turn, causes both necrotic cell death and activation of the hypoxia transcription factor HIF-1α. Herewith, we propose the hypothesis that both cell death and hypoxia represent two important events for the pathogenesis of damage and progression of amyloidoses. In fact, molecules released by necrotic cells activate inflammatory cells from one side while binding to HIF-1α-dependent membrane receptors expressed on hypoxic parenchymal cells on the other side. This latter event generates a signaling cascade triggering NFκB activation and chronic inflammation. Finally, we also suggest that this scenario, once proved and detailed, might suggest important targets for new therapeutic interventions.
UR - http://www.scopus.com/inward/record.url?scp=85070622105&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070622105&partnerID=8YFLogxK
U2 - 10.1155/2019/7935310
DO - 10.1155/2019/7935310
M3 - Review article
C2 - 31346362
AN - SCOPUS:85070622105
VL - 2019
SP - 1
EP - 11
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
SN - 1942-0900
M1 - 7935310
ER -