PMID- 10809400
OWN - NLM
STAT- MEDLINE
DCOM- 20000721
LR  - 20151026
IS  - 0300-9564 (Print)
IS  - 0300-9564 (Linking)
VI  - 107
IP  - 1
DP  - 2000
TI  - Cell death mechanisms in Parkinson's disease.
PG  - 1-29
AB  - OBJECTIVE: While the causes of neuronal death in Parkinson's disease (PD) and 
      other neurodegenerative disorders are still unknown, several mechanisms are under 
      discussion: programmed vs. passive cell death (apoptosis vs. necrosis), mainly 
      based on conflicting results on the rare presence or absence of DNA fragmentation 
      in substantia nigra neurons using the in situ DNA-labeling (TUNEL) method. 
      DESIGN/METHODS: In 4 cases of Parkinson's disease (PD), 2 cases of Dementia with 
      Lewy bodies (DLB) and 3 age-matched controls, the TUNEL/ISEL method was used to 
      detect DNA fragmentation in substantia nigra locus coeruleus and cerebral cortex 
      [method by Gold et al. (1994)]. In addition, immunohistochemistry was performed 
      for an array of apoptosis-related proteins, i.e. the recently described apoptosis 
      specific protein cJun/AP1 (ASP), the proto-oncogenes c-Jun, c-Jun AP1, Bcl2, Bax, 
      Bcl-x, p53, CD 95 (Fas/Apo-1), activated caspase 3, several heat shock proteins 
      (alpha-B crystallin, ubiquitin), and alpha-synuclein. RESULTS: None of the cases 
      of PD, DLB, and controls showed convincing TUNEL-positivity nor morphologic signs 
      of apoptosis in nigral, locus coeruleus or cortical neurons with or without Lewy 
      bodies but variable numbers of TUNEL-positive astrocytes and microglial cells in 
      substantia nigra of PD and DLB. There were no significant differences in the 
      expression of c-Jun, ASP, Bcl-2, Bax, and Bcl-x in substantia nigra neurons 
      between PD, DLB, and controls nor between cortical and subcortical neurons with 
      and without Lewy bodies. No expression of p53, and activated caspase 3, or any of 
      the examined stress proteins was seen in neurons, while reactive astroglia and 
      microglia were decorated by antibodies to Bcl-2, Bax, alpha-B-crystallin and 
      less, to Bcl-x and caspase 3. Lewy bodies, dystrophic neurites and axonal 
      spheroids, all being negative for the applied apoptosis regulating proteins, 
      showed strong expression of the examined stress proteins and of alpha-synuclein. 
      CONCLUSIONS: These findings which are in line with previous results in 
      Alzheimer's disease (Stadelmann et al., 1998) and Parkinson's disease (Banati et 
      al., 1999) suggest that mechanisms distinct from classical apoptosis play a 
      central role in the pathogenesis of PD and related neurodegenerative diseases. 
      Further studies are warranted to elucidate the intracellular cascade of events 
      leading to cell death in these disorders showing slow progression over many 
      years.
FAU - Jellinger, K A
AU  - Jellinger KA
AD  - Ludwig Boltzmann Institute of Clinical Neurobiology, Psychiatric Hospital, 
      Vienna, Austria. kurt.jellinger@univie.ac.at
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Austria
TA  - J Neural Transm (Vienna)
JT  - Journal of neural transmission (Vienna, Austria : 1996)
JID - 9702341
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Nerve Tissue Proteins)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal
MH  - Apoptosis/*physiology
MH  - Brain/*pathology
MH  - Brain Chemistry/physiology
MH  - Cytoskeleton/metabolism
MH  - DNA Fragmentation/physiology
MH  - DNA Repair/physiology
MH  - Female
MH  - Heat-Shock Proteins/analysis/immunology/metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Middle Aged
MH  - Nerve Degeneration/*pathology
MH  - Nerve Tissue Proteins/analysis/immunology/metabolism
MH  - Parkinson Disease/*pathology
EDAT- 2000/05/16 09:00
MHDA- 2000/08/01 11:00
CRDT- 2000/05/16 09:00
PHST- 2000/05/16 09:00 [pubmed]
PHST- 2000/08/01 11:00 [medline]
PHST- 2000/05/16 09:00 [entrez]
AID - 10.1007/s007020050001 [pii]
AID - 10.1007/s007020050001 [doi]
PST - ppublish
SO  - J Neural Transm (Vienna). 2000;107(1):1-29. doi: 10.1007/s007020050001.