Neuroprotective possibilities for Huntington's disease

被引:9
作者
Emerich, DF [1 ]
机构
[1] Alkermes Inc, Cambridge, MA 02139 USA
关键词
animal models; caspase; ciliary neurotrophic factor; creatine; huntingtin; Huntington's disease; neuroprotection;
D O I
10.1517/14712598.1.3.467
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Huntington's disease (HD) is a devastating genetic disorder. Despite the absence of effective therapy, there has been an explosion in interest for developing treatment strategies aimed at lessening or preventing the neuronal death that occurs in this disease. In large part, the renewed interest in neuroprotective strategies has been spurred by our increasing understanding of the genetic and molecular events that drive the underlying neuropathology of HD. This escalating understanding of the biological underpinnings of HD is derived from several convergent sources represented by investigators with clinical, genetic, molecular, physiological and neurobehavioural backgrounds. The diversity of data being generated has, in turn, produced a unique time in HD research where an impressive number of potential therapeutics are coming to the forefront. This review outlines several of these possibilities including the use of intracerebrally delivered neurotrophic factors, pharmacologically altering cellular energy production, the use of antiglutamatergic drugs, the use of caspase inhibitors and inhibitors of protein aggregation. This review also touches on the interesting possibility of whether or not the neurodegeneration in HD is at least partially reversible in nature. All of these possibilities are highlighted in the context that HD is a neurodegenerative disorder in which genetic detection provides a clear and unequivocal opportunity for neuroprotection.
引用
收藏
页码:467 / 479
页数:13
相关论文
共 78 条
  • [1] ABNORMALITIES OF STRIATAL PROJECTION NEURONS AND N-METHYL-D-ASPARTATE RECEPTORS IN PRESYMPTOMATIC HUNTINGTONS-DISEASE
    ALBIN, RL
    YOUNG, AB
    PENNEY, JB
    HANDELIN, B
    BALFOUR, R
    ANDERSON, KD
    MARKEL, DS
    TOURTELLOTTE, WW
    REINER, A
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1990, 322 (18) : 1293 - 1298
  • [2] PREFERENTIAL LOSS OF STRIATO-EXTERNAL PALLIDAL PROJECTION NEURONS IN PRESYMPTOMATIC HUNTINGTONS-DISEASE
    ALBIN, RL
    REINER, A
    ANDERSON, KD
    DURE, LS
    HANDELIN, B
    BALFOUR, R
    WHETSELL, WO
    PENNEY, JB
    YOUNG, AB
    [J]. ANNALS OF NEUROLOGY, 1992, 31 (04) : 425 - 430
  • [3] ALTERNATIVE EXCITOTOXIC HYPOTHESES
    ALBIN, RL
    GREENAMYRE, JT
    [J]. NEUROLOGY, 1992, 42 (04) : 733 - 738
  • [4] [Anonymous], NEURODEGENERATIVE DI
  • [5] Are there multiple pathways in the pathogenesis of Huntington's disease?
    Aronin, N
    Kim, M
    Laforet, G
    DiFiglia, M
    [J]. PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES, 1999, 354 (1386) : 995 - 1003
  • [6] CAG REPEAT SIZE AND CLINICAL PRESENTATION IN HUNTINGTONS-DISEASE
    ASHIZAWA, T
    WONG, LJC
    RICHARDS, CS
    CASKEY, CT
    JANKOVIC, J
    [J]. NEUROLOGY, 1994, 44 (06) : 1137 - 1143
  • [7] Neuroprotective gene therapy for Huntington's disease using a polymer encapsulated BHK cell line engineered to secrete human CNTF
    Bachoud-Lévi, AC
    Déglon, N
    Nguyen, JP
    Bloch, J
    Bourdet, C
    Winkel, L
    Rémy, P
    Goddard, M
    Lefaucheur, JP
    Brugières, P
    Baudic, S
    Cesaro, P
    Peschanski, M
    Aebischer, P
    [J]. HUMAN GENE THERAPY, 2000, 11 (12) : 1723 - 1729
  • [8] Bates GP, 2000, CONT NEUROS, P355
  • [9] Beal MF, 1997, MOL ASPECTS MED, V18, pS169
  • [10] BEAL MF, 1991, J NEUROSCI, V11, P1649