Apoptosis modulators in the therapy of neurodegenerative diseases

摘要: Apoptosis is a prerequisite to model the developing nervous system. However, an increased rate of cell death in adult system underlies neurodegenerative disease and hallmark multiple sclerosis (MS) Alzheimer's- (AD), Parkinson- (PD), or Huntington's (HD). Cell surface receptors (e.g., CD95/APO-1/Fas; TNF receptor) their ligands (CD95-L; TNF) as well evolutionarily conserved mechanisms involving proteases, mitochondrial factors (e.g. , Bcl-2-related proteins, reactive oxygen species, membrane potential, opening permeability transition pore) p53 participate modulation execution death. Effectors comprise oxidative stress, inflammatory processes, calcium toxicity survival factor deficiency. Therapeutic agents are being developed interfere with these events, thus conferring potential be neuroprotective. In this context, drugs anti-oxidative properties, e.g., flupirtine, N-acetylcysteine, idebenone, melatonin, but also novel dopamine agonists (ropinirole pramipexole) have been shown protect neuronal cells from apoptosis suggested for treating disorders like AD PD. Other non-steroidal anti-inflammatory (NSAIDs) partly inhibit cyclooxygenase (COX) expression, having positive influence on clinical expression AD. Distinct cytokines, growth related drug candidates, nerve (NGF), members transforming factor-beta (TGF-beta ) superfamily, differentiation 5 (GDF-5), tyrosine hydroxylase dopaminergic neurones apoptosis. Furthermore, peptidergic cerebrolysin has found support vitro vivo. Treatment protease inhibitors targets prevent DNA fragmentation PD patients. Finally, CRIB (cellular replacement by immunoisolatory biocapsule) auspicious gene therapeutical approach human NGF secretion, which cholinergic when implanted brain. This review summarises evaluates aspects anti-apoptotic concepts pharmacological intervention including approaches currently proposed utilised treat diseases.