The Fiber-Optic Club

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The Fiber-Optic Club

• Protein misfolding and amyloid diseases

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Proteins
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Protein folding
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Models of protein folding
Christian AnfinsenNobel Prize 1972
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Protein misfolding and disease

• Loss of function or Gain of toxicity
• Genetic or Sporadic

(some proteins are natively unfolded)
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Amyloid Fibril Formation

• A major group of protein misfolding diseases
• A self-assembly process of a single protein that
  leads to the formation of large and well-ordered
  fibrillar structures
• Formed by a verity of proteins
• The amyloids are cytotoxic and cell destruction
  is co-localized with amyloid deposits

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Amyloid fibrils are the hallmark of major human
disorders of the current era

• Fibrils of different origins share common
  characteristic, however there is no homology
  between amyloid-forming proteins
• The diseases are predominantly sporadic and
  manifested late in life

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Alzheimers disease
About 5 of men and women ages 65 to 74 have
Alzheimer's disease , and nearly half of those
age 85 and older may have the disease. Official
NIH estimation
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  ????? ????? ???? ????? ?-CJD ????

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• ???? ?-90 ???????
• ????? ????? ?????? ?-vCJD

???? ?????? ????????? ?? CJD (???? ?????
?????????, ?????????? ????, ?????? ????? ????)
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?-28.10.2000
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????? ??????? (??????? ?-1984) ???? ????? ?????
????? ????? ?? ???????? ????? ???? ?-CJD
???? ????? ?-BSE ?????? "???? ???????"
???-??? ????? ?-CJD
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??? ???? ????? ????? CJD ????? ?? ???? ??????
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?"? ????? ?? ???? ????? (?"? ???? ????? ??
???)
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Amyloid fibrils are well-order structures at the
nanometric-scale
Sikorski et al., Structure, 2003
Jiménez et al., EMBO J., 1999
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The native protein undergoes a structural
transition into ?-sheet structures
Soto (2003) Nature reviews
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Amyloid formation is a process of molecular
recognition and self-assembly
Gazit (2002) Angew. Chem.
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Fibrils or prefibrillar oligomers?
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Amyloid plaques in the eye
Early detection of Alzheimers using
photoacoustic spectroscopy