Lysosomal storage diseases in Europe: problem of neurodegeneration and the new trends in therapeutic interventions
The new tendencies in study of lysosomal storage diseases in Europe with a special interest in autophagy, neuropathology and the new therapeutic technologies were considered. Decrease of autophagy contributes usually to accumulation of misfolded proteins, stress of ER (UPR), protein aggregation and formation of neuropathological signs. This is shown for influence of Gaucher disease (defect of β-glucocerebrosidase) on formation of Parkinson disease. Storage syndrome as whole and cellular senescence hinder activity of autophagy and endocytosis. Therefore therapeutic/neuroprotective interventions for treatment of lysosomal diseases were connected with stimulation of the own cellular protective mechanisms such as autophagy, activity of proteins TFEB, Hsp70. Additionally to neuroprotection the positive effect of enhanced autophagy on prevention of bone defects was shown also. Considerable progress was achieved in gene therapy of lysosomal diseases by application of adenovirus- and lentivirus-associated constructions of wild type of defective enzymes or their promoters, and the best results were obtained with intracranial mode of injection. The other ways of successful therapeutic interventions were considered also.
About Authors (Correspondence):
Pupyshev A.B. – candidate of biological sciences, senior researcher of central research laboratory, e-mail: email@example.com