Over the years, biological drugs have evolved and have made breakthroughs in diseases associated with extracellular proteins. However, intracellular proteins that cause disease progression are still largely inaccessible. Examples of diseases that are caused by an intracellular aggregation of proteins are neurodegenerative diseases such as Parkinson's disease, Huntington's disease (HD), and Alzheimer's disease (AD). The purpose of the work is to find a strategy to reach the neurons intracellularly. The goal is to be able to design a biological drug that enters the neuron by investigating different uptake mechanisms. A systematic review of 43 published studies was reviewed, and the results could be obtained. All result presents data from different receptors, cell-penetrating peptides, and adeno-associated viruses (AAV) that were examined. It showed that there are advantages and disadvantages with all the uptake mechanisms. There are risks of side effects for each uptake mechanism, and further studies are required to consider the risk. AAV2 and the neuron-specific receptors lack specific information about their mechanism, but there is a high potential to develop these strategies. Both AVV and the neuron-specific receptors provide specific uptake into tissues.