Endogenous aggregates of amyloidogenic cystatin C variant are removed by THP-1 cells in vitro and induce differentiation and a proinflammatory response.

[hereditary cerebral hemorrhage with amyloidosis]

A mutation in the human cystatin C gene leads to familial cerebral amyloid angiopathy . This disease is known as "hereditary cerebral hemorrhage with amyloidosis -Icelandic type " or "hereditary cystatin C amyloid angiopathy ." The mutant cystatin C protein forms aggregates and amyloid , within the central nervous system almost exclusively in connection with the vascular system . It was not known whether immune cells could remove mutant cystatin C protein aggregates . Ex vivo mutant cystatin C protein aggregates , both in solution and dried onto a glass surface , induced adhesion to the substrate , differentiated the THP-1 monocyte cell line and led to a proinflammatory response . Aggregates were also taken up by both THP-1 cells and THP-1 derived macrophages . These are the same responses induced by other amyloidogenic protein species , such as amyloid β protein and amylin , supporting the model of all amyloidogenic proteins being toxic due to common structural motifs . Proinflammatory response induced by the ex vivo mutant cystatin C protein aggregates suggests that vascular inflammation plays an important role in hereditary cerebral hemorrhage with amyloidosis -Icelandic type . Ex vivo protein aggregates of cystatin C might better model cellular behavior than in vitro-generated aggregates or supplement in vitro material .

Diseases
Validation

Diseases presenting "central nervous system" symptom

22q11.2 deletion syndrome

adrenomyeloneuropathy

alexander disease

aniridia

aromatase deficiency

canavan disease

child syndrome

classical phenylketonuria

congenital toxoplasmosis

cowden syndrome

cushing syndrome

cystinuria

dracunculiasis

erdheim-chester disease

fabry disease

gm1 gangliosidosis

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

kabuki syndrome

kallmann syndrome

kindler syndrome

krabbe disease

lamellar ichthyosis

legionellosis

liposarcoma

malignant atrophic papulosis

monosomy 21

neonatal adrenoleukodystrophy

phenylketonuria

proteus syndrome

scrub typhus

severe combined immunodeficiency

sneddon syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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