Gradual accumulation of amyloid beta protein (Aβ) in extracellular spaces and phosphorylated tau (p-tau) intracellularly are the hall mark pathologies in Alzheimer’s disease (AD). Protein degradation machinery, such as auto phagylysosomal pathway play a pivotal role to dispose these aggregates from the cell. Deficiency of autophagy can cause neurodegeneration, while activation of autophagyis protective against different proteinopathies. These pathways become dysfunctional or dysregulated in AD. Therefore, restorationor maintenance of these systems is essential and could be a promising strategy to remove Aβ-aggregates from neurons to prevent or delay further neurodegeneration in AD. Pharmacological manipulations, including use of natural compounds could be promising to keep them active. In this short review, the mechanistic details of the role of autophagy lysosomal pathway (ALP) are discussed, along with promising role of curcumin, a natural anti-amyloid polyphenol to boost this system. This brief and comprehensive review article should help the researcher to understand basic mechanism of role of ALP in AD and other neurological diseases, which are associated with protein misfolding.