Section 1.3.4.3.5. Neurological disorders

Even a quick glance at Table 1.3.4.5 shows that crystallography contributes to new therapeutics for numerous human afflictions and diseases. Yet there are major gaps in our understanding of protein functions, in particular of those involved in development and in neurological functions. These proteins are the target of many drugs obtained by classical pre-crystal-structure methods. These proven drug targets are very often membrane proteins involved in neuronal functions, and the diseases concerned are some of the most prevalent in mankind. A non-exhaustive list includes cerebrovascular disease (strokes), Parkinson's, epilepsy, schizophrenia, bipolar disease and depression.

Some of these diseases are heart-breaking afflictions, where parents have to accept the suicidal tendencies of their children, often with fatal outcomes; where partners have to endure the tremendous mood swings of their bipolar spouses and have to accept extreme excesses in behaviour; where a happy evening of life is turned into the gradual and sad demise of human intellect due to the progression of Alzheimer's, or to the loss of motor functions due to Parkinson's, or into the tragic stare of a victim of deep depression. Human nature, in all its shortcomings, has the tendency to try to help such tragic victims, but drugs for neurological disorders are rare, drug regimens are difficult to optimize and the commitment to follow a drug regimen – often for years, and often with major side effects – is a next to impossible task in many cases. New, better drugs are urgently needed and hence the structure determinations of the `molecules of the brain' are major scientific as well as medical challenges of the next decades. Such molecules will shed light on some of the deepest mysteries of humanity, including memory, cognition, desire, sleep etc. At the same time, such structures will provide opportunities for treating those suffering from neurodegenerative diseases due to age, genetic disposition, allergies, infections, traumas and combinations thereof. Such `CNS protein structures' are one of the major challenges of biomacromolecular crystallography in the 21st century.