| Project/Area Number |
06670679
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE |
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Principal Investigator |
NAKANO Imaharu TOKYO MET.INST.FOR NEUROSCI,NEUROPATHOLOGY,DIRECTOR, 神経病理学研究部門, 副参事 (40092423)
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| Co-Investigator(Kenkyū-buntansha) |
ODA Masaya TOKYO NEUROL HOSP PATHOLOGY AND LABORATORY MEDICINE,DIRECTOR, 検査科, 部長
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | AMYOTROPHIC LATERAL SCLEROSIS / UBIQUITIN / LYSOSOME / ELECTRON MICROSCOPY / INCLUSION / LOWER MOTOR NEURON / hyaline inclusion / skein-like inclusion |
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| Research Abstract |
LOWER MOTOR NEURONS (LMNs) IN AMYOTROPHIC LATERAL SCLEROSIS (ALS) CONTAIN SEVERAL TYPES OF CYTOPLASMIC INCLUSIONS,AMONG WHICH SKEIN-LIKE INCLUSIONS (SLIs) AND HYALINE INCLUSIONS (OR ROUND INCLUSIONS [RIs]) ARE UBIQUITINATED.UBIQUITIN IS A CYTOPLASMIC PROTEIN REQUIRED FOR DEGRADATION TO AMINO ACIDS OF VARIOUS PROTEINS THAT HAVE DEGENERATED OR BECOME UNNECESSARY.THERFEORE,UBIQUITINATION OF SOME CYTOPLASMIC PROFILES MEANS THAT THE DEGRADATION SYSTEM USING UBIQUITIN IN ABORTED.THUS,IT IS LIKELY THAT SLIs AND RIs WHICH ARE BOTH UBIQUITINATED HAVE ESCAPED UBIQUITIN DEGRADATION SYSTEM,BUT THEIR FINAL DESTINATION IN NOT KNOWN.
IN THIS STUDY,WE DETECTED 5-6 NEURONS CONTAINING SLIs AND/OR RIs BY OBSERVING SPINAL CORD LMNs OF OVER 20 CASES OF ALS.SLIs ARE BUNDLES OF ABOUT 15NM ABNORMAL FILAMENTS ; THEY WERE USUALLY EXPOSED TO THE CYTOSOL WITHOUT LIMITING MEMBRANES,WHILE SOME WERE SURROUNDED BY FLAT CISTERNS TO VARIOUS DEGREES.THE CISTERNS QUITE RESEMBLED THOSE WHICH ARE SEEN IN THE EARLY STAGES OF FORMATION OF GRANULOVACUOLAR DEGENERATION IN THE PYRAMIDAL NEURONS OF THE AMMON'S HORN.ON THE OTHER HAND,RIs.WHICH WERE COMPOSED OF NEUROFILAMENTS,ABNORMAL FILAMENTS SIMILAR TO THOSE OF SLIs, AND VARIOUS AGGREGATES OF ELECTRON DENSE GRANULES,ACCUMULATED FLAT CISTERNS AND AUTOLYOSOME-LIKE PROFILES AROUND THEM TO VARIOUS DEGREES.
THE ABOVE FINDINGS INDICATE THAT AT LEAST SOME OF UBIQUITINATED INCLUSIONS IN ALS LOWER MOTOR NEURONS ARE TREATED BY THE LYSOSOMAL SYSTEM.
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