Amyloid Diseases
Amyloid diseases, also called amyloidoses, are characterized by the deposition of cross-β-sheet amyloid fibrils composed of misfolded and/or misassembled proteins. More than 30 human proteins are known to potentially undergo such abnormal aggregation causing degenerative disorders. The resulting illnesses are distinguished by the specific proteins involved and include Alzheimer's and Parkinson' diseases, Creutzfeldt–Jakob disease, type II diabetes, and a number of systemic amyloidoses. The current treatments are only symptomatic and do not decelerate or prevent the progression of these diseases. Furthermore, the diagnosis is often made at advanced stages, hence reducing the efficacy of the drugs currently available. Therefore, new disease-modifying therapies and efficient systems for early diagnosis are urgently required.
- Alzheimer's disease (AD) is estimated to currently affect more than 48 million people worldwide according to WHO, and 152 million individuals will be affected by 2050. To date, the treatments available only lessen the symptoms and may help extend the autonomy of AD patients; None of them are capable of slowing down or stopping the progression of the disease.
AD is characterized by two main hallmarks, namely the extracellular deposition of amyloid-β
(Aβ) aggregates (senile plaques) and the intracellular formation of fibrillar aggregates of the microtubule-associated protein tau. Eventually, both the amyloid deposits and the neurofibrillary tau tangles cause irreversible brain damages, leading to brain atrophy and loss of cognitive function.
- Parkinson's disease (PD) is the second-most common neurodegenerative disorder that affects about 3% of the population aged 65 years and over. PD can not be cured but some medications (mostly dopaminergic drugs) help control the symptoms, managing problems with walking, movement and tremor.
The neuropathological hallmarks of PD are neuronal loss in the substantia nigra, causing striatal dopamine deficiency, and the intracellular formation of α-synuclein
aggregates.
- Creutzfeldt–Jakob disease (CJD) is a rare degenerative, fatal brain disorder that affects about 10,000 individuals per year worldwide. There is currently no treatment to cure or control CJD; only some opiate drugs are prescribed to help relieve pain, and clonazepam or sodium valproate may be given to the patients to relieve myoclonic symptoms.
CJD is caused by abnormal forms of normal cellular proteins called prions. The normal, harmless prion is usually designatedas
PrPC
(C = cellular) and the abnormal, infectious form is PrPSc
(Sc = prototypical prion disease–scrapie). In acquired CJD, PrPSc
comes from outside the body and affects normal PrPC, converting it into the infectious form. In hereditary CJD, infectious prions can be generated through mutation of the gene for the body’s normal prion protein. In sporadic CJD, the generation of infectious prions results from an error of the cell machinery that produce proteins. In all cases, once abnormal PrPSc
are produced, they form aggregates, which lead to nerve cell loss and brain damage.
At nanoBIC, we are designing and preparing selective (fluorescent) copper chelators and conjugating them to nanoparticles. Such chelator-decorated nanoparticles allow the detection of copper and may also favor the re-establishment of normal metallo-trafficiking that is lost in amyloidoses, therefore reducing oxidative stress (theranostics). We are developing diagnostic systems based on both superparamagnetic and gold nanoparticles for the detection of infinitesimal quantities of pathogenic amyloids in biological fluids (early diagnosis).