TY - JOUR
T1 - Huntington's disease
T2 - Pathological mechanisms and therapeutic strategies
AU - Ramaswamy, Shilpa
AU - Shannon, Kathleen M.
AU - Kordower, Jeffrey H.
PY - 2007
Y1 - 2007
N2 - Huntington's disease (HD) is a devastating neurodegenerative disorder that occurs in patients with a mutation in the huntingtin or IT15 gene. Patients are plagued by early cognitive signs, motor deficits, and psychiatric disturbances. Symptoms are attributed to cell death in the striatum and disruption of cortical-striatal circuitry. Mechanisms of cell death are unclear, but processes involving mitochondrial abnormalities, excitotoxicity, and abnormal protein degradation have been implicated. Many factors likely contribute to neuron death and dysfunction, and this has made it difficult to systematically address the pathology in HD. Pharmaceutical therapies are commonly used in patients to treat disease symptoms. These have limited benefit and do not address the inexorable disease progression. Several neuroprotective therapies are being evaluated in animal models of HD as well as in clinical trials. Similarly, cell replacement strategies such as fetal transplantation have been used in the clinic with minimal success, making future cell replacement strategies such as stem cell therapy uncertain. This review describes the disease pathology in HD and addresses many of the past and emerging therapeutic strategies.
AB - Huntington's disease (HD) is a devastating neurodegenerative disorder that occurs in patients with a mutation in the huntingtin or IT15 gene. Patients are plagued by early cognitive signs, motor deficits, and psychiatric disturbances. Symptoms are attributed to cell death in the striatum and disruption of cortical-striatal circuitry. Mechanisms of cell death are unclear, but processes involving mitochondrial abnormalities, excitotoxicity, and abnormal protein degradation have been implicated. Many factors likely contribute to neuron death and dysfunction, and this has made it difficult to systematically address the pathology in HD. Pharmaceutical therapies are commonly used in patients to treat disease symptoms. These have limited benefit and do not address the inexorable disease progression. Several neuroprotective therapies are being evaluated in animal models of HD as well as in clinical trials. Similarly, cell replacement strategies such as fetal transplantation have been used in the clinic with minimal success, making future cell replacement strategies such as stem cell therapy uncertain. This review describes the disease pathology in HD and addresses many of the past and emerging therapeutic strategies.
KW - Cell death
KW - Huntington's disease
KW - Symptoms
KW - Therapies
UR - http://www.scopus.com/inward/record.url?scp=34250659732&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250659732&partnerID=8YFLogxK
U2 - 10.3727/000000007783464687
DO - 10.3727/000000007783464687
M3 - Article
C2 - 17503740
AN - SCOPUS:34250659732
SN - 0963-6897
VL - 16
SP - 301
EP - 312
JO - Cell Transplantation
JF - Cell Transplantation
IS - 3
ER -