**5. Conclusions**

Alzheimer's disease is a debilitating neurodegenerative condition and is projected to be a major risk factor for global population by the year 2050 [98]. One of the key theories, known as "amyloid cascade hypothesis" postulates that oligomerization of amyloid-β (Aβ) in brain is the key pathological event in AD [99]. Although complete explanation of causation in AD is yet to be established, it has been universally accepted that amyloidosis (perhaps provoked by environmental factors) plays a crucial role in AD progression [99–101]. Conformational alterations in Aβ which lead to its conversion from soluble peptide to insoluble aggregates are considered as a key mechanism in pathogenesis of neurodegenerative diseases such as AD [102]. Early amyloid aggregates can act as biomarkers in most dementia related maladies and associate observed clinical symptoms to underlying pathophysiological mechanisms. Till date, we do not have any therapeutic solution for aggregation of amyloids. Current gold-standard biomarkers in neurodegeneration are neuroimaging systems of degeneration and detectable clinical symptoms represent pathological changes causing irreversible damage to nervous system [33, 36]. Success of theranostic efforts will rely on rational drug design based on a proper understanding of molecular structures and mechanisms involved in aggregation. Aβ mediates AD pathology through direct inhibition of neuronal interactions and signaling cascades, and triggers oxidative stress in the process. Here we have discussed mechanisms of action of amyloid chaperones with focus on Aβ chaperones to better understand their modus operandi. Apart from the protein quality control machinery and housekeeping complexes responsible for maintaining general proteostasis, we have discussed importance of other endogenous chaperones which step up in time of crisis, often as response to stress stimuli. Proteins such as L-PGDS, clusterin, α2M have are involved in many physiological processes, with elusive function as amyloid chaperones. These proteins can provide alternative mechanisms to control amyloid aggregates in events of failure of intracellular Hsp complexes and proteasome machinery. Additionally, their affinity to redox active components may provide additional protective mechanisms against Aβ mediated oxidative stress.

**201**

*Neuroprotective Function of Non-Proteolytic Amyloid-β Chaperones in Alzheimer's Disease*

*DOI: http://dx.doi.org/10.5772/intechopen.84238*

Authors declare no conflict of interest.

ALS amyotrophic lateral sclerosis APP amyloid precursor protein

DARR dipolar assisted rotation resonance

REDOR rotational echo double resonance

TEM transmission electron microscopy

UPR unfolded protein response UPS ubiquitin proteasome system

ssNMR solid state nuclear magnetic resonance

TSE transmissible spongiform encephalopathy

**Conflict of interest**

**Abbreviations**

Aa amino acid

Aβ amyloid-β

AD Alzheimer's disease

CNS central nervous system CSF cerebrospinal fluid

EM electron microscopy HD Huntington disease HNE hydroxy-2,3-nonenal Hsc heat shock cognate Hsp heat shock protein HSR heat shock response IAPP islet amyloid polypeptide NMDA N-methyl-D-aspartate NMR nuclear magnetic resonance OHDG 8-hydroxy-2′-deoxyguanosine

PD Parkinson's disease PDB protein data bank PrP prion protein

ROS reactive oxygen species SOD superoxide dismutase

T2D type II diabetes

Ub ubiquitin

αS α synuclein

*Neuroprotective Function of Non-Proteolytic Amyloid-β Chaperones in Alzheimer's Disease DOI: http://dx.doi.org/10.5772/intechopen.84238*
